Trial Outcomes & Findings for An Open-Label, Long-Term Study of Oral Treprostinil in Subjects With Pulmonary Arterial Hypertension (NCT NCT01560637)

NCT ID: NCT01560637

Last Updated: 2022-06-02

Results Overview

All subjects who received oral treprostinil in TDE-PH-311 were included in the Safety population. All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit. The overall summary of AEs includes the number of subjects with any AE, the number of subjects with any study drug-related AEs, the number of subjects with AEs leading to study drug withdrawal, the number of subjects with any serious AEs, the number of subjects with any severe AEs, and the number of subjects with any study drug-related severe/serious AEs. AEs were coded using the Medical Dictionary for Regulatory Activities.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 471 participants
• Primary outcome timeframe: Participants will be followed every 12 weeks, at minimum, until they discontinue the study or the study is discontinued by the sponsor or for a period up to 2.5 years
• Results posted on: 2022-06-02

Participant Flow

Participant milestones

Measure	UT-15C Open label access UT-15C (treprostinil diethanolamine): UT-15C sustained release oral tablet for three times daily administration
Overall Study STARTED	470
Overall Study COMPLETED	272
Overall Study NOT COMPLETED	198

Reasons for withdrawal

Measure	UT-15C Open label access UT-15C (treprostinil diethanolamine): UT-15C sustained release oral tablet for three times daily administration
Overall Study Adverse Event	63
Overall Study Death	69
Overall Study Lost to Follow-up	8
Overall Study Protocol Violation	8
Overall Study Withdrawal by Subject	24
Overall Study Progressive Disease	20
Overall Study Other Reason Not Specified	6

Baseline Characteristics

An Open-Label, Long-Term Study of Oral Treprostinil in Subjects With Pulmonary Arterial Hypertension

Baseline characteristics by cohort

Measure	UT-15C n=470 Participants Open label access UT-15C (treprostinil diethanolamine): UT-15C sustained release oral tablet for three times daily administration
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	398 Participants n=5 Participants
Age, Categorical >=65 years	72 Participants n=5 Participants
Age, Continuous	47.2 years STANDARD_DEVIATION 15.1 • n=5 Participants
Sex: Female, Male Female	374 Participants n=5 Participants
Sex: Female, Male Male	96 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	135 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	334 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	213 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants
Race (NIH/OMB) White	245 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Etiology of Pulmonary Arterial Hypertension (PAH) Idiopathic of Heritable PAH	299 Participants n=5 Participants
Etiology of Pulmonary Arterial Hypertension (PAH) Collagen Vascular Disease	114 Participants n=5 Participants
Etiology of Pulmonary Arterial Hypertension (PAH) HIV Infection	8 Participants n=5 Participants
Etiology of Pulmonary Arterial Hypertension (PAH) Congenital Heart Defect	38 Participants n=5 Participants
Etiology of Pulmonary Arterial Hypertension (PAH) Other	11 Participants n=5 Participants
Background PAH Therapy at Randomization in Parent Study Phosphodiesterase Type 5 Inhibitor (PDE5-I) Alone/Soluble Guanylate Cyclase (sGC) Stimulator Alone	348 Participants n=5 Participants
Background PAH Therapy at Randomization in Parent Study Endothelin Receptor Antagonist (ERA) alone	122 Participants n=5 Participants
Time since Diagnosis	3.16 years STANDARD_DEVIATION 2.69 • n=5 Participants
6-Minute Walk Distance (6MWD) at Baseline	392.0 meters STANDARD_DEVIATION 128.1 • n=5 Participants
WHO Functional Class at Baseline I	41 Participants n=5 Participants
WHO Functional Class at Baseline II	226 Participants n=5 Participants
WHO Functional Class at Baseline III	182 Participants n=5 Participants
WHO Functional Class at Baseline IV	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: Participants will be followed every 12 weeks, at minimum, until they discontinue the study or the study is discontinued by the sponsor or for a period up to 2.5 years

Population: All subjects who received oral treprostinil in TDE-PH-311 were included in the Safety population.

All subjects who received oral treprostinil in TDE-PH-311 were included in the Safety population. All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit. The overall summary of AEs includes the number of subjects with any AE, the number of subjects with any study drug-related AEs, the number of subjects with AEs leading to study drug withdrawal, the number of subjects with any serious AEs, the number of subjects with any severe AEs, and the number of subjects with any study drug-related severe/serious AEs. AEs were coded using the Medical Dictionary for Regulatory Activities.

Outcome measures

Measure	UT-15C n=470 Participants Open label access UT-15C (treprostinil diethanolamine): UT-15C sustained release oral tablet for three times daily administration
Number of Adverse Events Adverse Event	450 events
Number of Adverse Events Study Drug Related AE	362 events
Number of Adverse Events AE Leading to Study Drug Withdrawal	126 events
Number of Adverse Events Serious AE	206 events
Number of Adverse Events Severe AE	182 events
Number of Adverse Events Study Drug Related Severe AE	67 events
Number of Adverse Events Study Drug Related Serious AE	37 events

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: All participants are subjects who received oral treprostinil in TDE-PH-311. For post-Baseline visits, only subjects with measurements at Baseline and the corresponding visit are included. Baseline is defined as the last measurement prior to the first dose of oral treprostinil in TDE-PH-311.

A summary of change from Baseline in 6MWD at Week 48 for the Safety Population is provided. The Safety Population is all subjects who received oral treprostinil in TDE-PH-311.

Outcome measures

Measure	UT-15C n=341 Participants Open label access UT-15C (treprostinil diethanolamine): UT-15C sustained release oral tablet for three times daily administration
Change in 6-Minute Walk Distance From Baseline	20.1 meters Standard Deviation 79.6

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: Safety Population (all subjects who received oral treprostinil in TDE-PH-311). For post-Baseline visits, only subjects with measurements at Baseline and the corresponding visit are included. Baseline is defined as the last measurement prior to the first dose of oral treprostinil in TDE-PH-311.

Change in Borg Dyspnea Score from at Week 48 is provided for the Safety Population (all subjects who received oral treprostinil in TDE-PH-311).

The Borg Dyspnea Scale is a 0 to 10 rated numerical score used to measure dyspnea as reported by the patient during submaximal exercise and was administered during six-minute walk testing (6MWT), one of the most common and frequently used measures to assess disease severity in PAH. The numbers on the scale are as follows: 0 (no shortness of breath [SOB]), 0.5 (very very slight SOB), 1 (very slight SOB), 3 (moderate SOB), 4 (somewhat severe SOB), 5 (severe SOB), 7 (very severe SOB), 9 (very very severe SOB), 10 (maximal SOB).

Outcome measures

Measure	UT-15C n=341 Participants Open label access UT-15C (treprostinil diethanolamine): UT-15C sustained release oral tablet for three times daily administration
Change in Borg Dyspnea Score From Baseline to Week 48	-0.49 score on a scale Standard Deviation 1.92

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: Safety Population was analyzed. Baseline is defined as the last measurement prior to the first dose of oral treprostinil in TDE PH 311.

Change from Baseline at Week 48 in WHO FC in the Safety Population (all subjects who received oral treprostinil in TDE-PH-311).

The World Health Organization functional classification (WHO-FC) is a clinician-rated assessment used widely to assess PAH severity and functioning.

Class I (least severe): Patients are without limitation of physical activity.

Class II: Patients are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope.

Class III: Marked limitation of physical activity. They are comfortable at rest.

Class IV (most severe): Inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure.

Outcome measures

Measure	UT-15C n=362 Participants Open label access UT-15C (treprostinil diethanolamine): UT-15C sustained release oral tablet for three times daily administration
Change From Baseline to Week 48 in WHO Functional Class	-0.2 score on a scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: Subjects in the Safety Population were analyzed. For post-Baseline visits, only subjects with measurements at Baseline and the corresponding visit are included. Baseline is defined as the last measurement prior to the first dose of oral treprostinil in TDE-PH-311.

Change in N-terminal pro-brain natriuretic peptide from Baseline at Week 48 for the Safety Population (any subject who received oral treprostinil in TDE-PH-311)

Outcome measures

Measure	UT-15C n=322 Participants Open label access UT-15C (treprostinil diethanolamine): UT-15C sustained release oral tablet for three times daily administration
Change in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Baseline to Week 48	-179.23 pg/mL Standard Deviation 1968.99

Adverse Events

UT-15C

Serious events: 206 serious events

Other events: 467 other events

Deaths: 74 deaths

Serious adverse events

Measure	UT-15C n=470 participants at risk Open label access UT-15C (treprostinil diethanolamine): UT-15C sustained release oral tablet for three times daily administration
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	12.1% 57/470 • Number of events 79 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Pneumonia	6.8% 32/470 • Number of events 39 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Right ventricular failure	4.7% 22/470 • Number of events 27 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiac failure	4.0% 19/470 • Number of events 25 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Septic shock	1.9% 9/470 • Number of events 9 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.7% 8/470 • Number of events 8 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Acute kidney injury	1.5% 7/470 • Number of events 8 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.5% 7/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Diarrhoea	1.3% 6/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Gastroenteritis	1.3% 6/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Hypotension	1.3% 6/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Anaemia	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Cholecystitis acute	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Respiratory tract infection	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Sepsis	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Urinary tract infection	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiac arrest	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiogenic shock	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Endocrine disorders Hyperthyroidism	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Syncope	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Appendicitis	0.64% 3/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Atrial fibrillation	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Atrial flutter	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations COVID-19	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations COVID-19 pneumonia	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiac failure congestive	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cor pulmonale	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Fluid overload	0.64% 3/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Multiple organ dysfunction syndrome	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Myocardial infarction	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Shock	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.64% 3/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Vomiting	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Abdominal pain	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Surgical and medical procedures Abortion induced	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Atrioventricular block complete	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Bronchitis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiac failure acute	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiopulmonary failure	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Catheterisation cardiac	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Cellulitis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Cerebrovascular accident	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Chest pain	0.43% 2/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Clostridium difficile colitis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Dehydration	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Electrolyte imbalance	0.43% 2/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Hand fracture	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hepatic function abnormal	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hypokalaemia	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Melaena	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Oedema	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Pericardial effusion	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Peritonitis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Pulmonary oedema	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Rash	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Renal failure	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Right ventricular dysfunction	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Sjogren's syndrome	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Sudden death	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Supraventricular tachycardia	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Thrombocytopenia	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Upper respiratory tract infection	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Abdominal distension	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Accidental overdose	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Acute abdomen	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Acute hepatic failure	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Acute myocardial infarction	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Acute pulmonary oedema	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Acute right ventricular failure	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Endocrine disorders Adrenocortical insufficiency acute	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Amaurosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Anaemia of malignant disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Aortic valve incompetence	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Arrhythmia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Arteriovenous fistula site haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Ascites	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Asthenia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Atrioventricular block	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Atrioventricular block second degree	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Bacteraemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Bacterial translocation	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Biliary tract disorder	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood creatinine increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Brain injury	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Breast mass	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiac failure chronic	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardio-respiratory arrest	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Chest discomfort	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Cholecystitis infective	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Cholestasis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Chronic kidney disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Coagulation time prolonged	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Colitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Coma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Congestive hepatopathy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cor pulmonale acute	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Coronary artery disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Delirium	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Diarrhoea infectious	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Disease progression	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Diverticulitis	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Diverticulum	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Endocrine ophthalmopathy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Enteritis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Enteritis infectious	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Erythropenia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Fall	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Fibrocystic breast disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Gangrene	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastric polyps	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastric varices haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastritis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastritis haemorrhagic	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastrointestinal disorder	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastrointestinal polyp haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastrointestinal vascular malformation haemorrhagic	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Generalised oedema	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Glomerulonephritis acute	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Gout	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Haematuria	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Haemolytic anaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Headache	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer recurrent	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hepatic cirrhosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hepatic encephalopathy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hepatic failure	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hepatitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.21% 1/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hyperglycaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hyperuricaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hypervolaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Ileus	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Infective exacerbation of bronchiectasis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Influenza	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Inguinal hernia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Intentional overdose	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Intermenstrual bleeding	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Intestinal obstruction	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Iron deficiency anaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Ischaemic stroke	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Large intestine polyp	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Liver injury	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Loss of consciousness	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Lower respiratory tract infection	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Lupus nephritis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Mechanical ileus	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Meningitis listeria	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Mental status changes	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Metabolic acidosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Metabolic encephalopathy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Muscle atrophy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Oedema peripheral	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Ophthalmic herpes zoster	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian adenoma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Ovarian cyst	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) POEMS syndrome	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Pancytopenia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Pelvic fluid collection	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Pelvic fracture	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Pericarditis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Peripheral arterial occlusive disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Pneumonia aspiration	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Pneumonia influenzal	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Portal hypertensive gastropathy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Presyncope	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Pulseless electrical activity	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Purpura	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Pyrexia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Rectal haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Renal vasculitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Road traffic accident	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Scleroderma renal crisis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Seizure	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Sialoadenitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Sinus tachycardia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Splenic rupture	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Staphylococcal sepsis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Subcapsular hepatic haematoma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Subdural haematoma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Sudden cardiac death	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Transaminases increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Tricuspid valve incompetence	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Tubulointerstitial nephritis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Urinary bladder polyp	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Urosepsis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Ear and labyrinth disorders Vertigo	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.

Other adverse events

Measure	UT-15C n=470 participants at risk Open label access UT-15C (treprostinil diethanolamine): UT-15C sustained release oral tablet for three times daily administration
Cardiac disorders Tachycardia	2.3% 11/470 • Number of events 16 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Anaemia	10.9% 51/470 • Number of events 55 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Thrombocytopenia	3.6% 17/470 • Number of events 19 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Iron deficiency anaemia	1.9% 9/470 • Number of events 11 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Leukopenia	1.7% 8/470 • Number of events 10 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Splenomegaly	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Coagulopathy	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Pancytopenia	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Anaemia of malignant disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Antiphospholipid syndrome	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Erythropenia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Haemolytic anaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Hyperglobulinaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Leukocytosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Lymphadenopathy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Microcytic anaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Neutropenia	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Neutrophilia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Normochromic normocytic anaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Splenic calcification	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders Splenic cyst	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Blood and lymphatic system disorders White blood cell disorder	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Palpitations	15.7% 74/470 • Number of events 81 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Right ventricular failure	8.3% 39/470 • Number of events 54 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiac failure	5.5% 26/470 • Number of events 34 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Atrial fibrillation	2.1% 10/470 • Number of events 11 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Atrial flutter	1.5% 7/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Supraventricular tachycardia	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiac arrest	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiogenic shock	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cor pulmonale	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Pericardial effusion	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Angina pectoris	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiac failure congestive	0.64% 3/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Extrasystoles	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Myocardial infarction	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Right ventricular dysfunction	0.64% 3/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Supraventricular extrasystoles	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Aortic valve incompetence	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Arteriosclerosis coronary artery	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Atrioventricular block	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Atrioventricular block complete	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Atrioventricular block second degree	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Bradycardia	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Bundle branch block right	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiac failure acute	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiopulmonary failure	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Coronary artery disease	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Right ventricular hypertrophy	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Sinus tachycardia	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Acute myocardial infarction	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Acute right ventricular failure	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Arrhythmia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Atrial tachycardia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Atrioventricular block first degree	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiac discomfort	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiac failure chronic	0.21% 1/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardio-respiratory arrest	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cardiomegaly	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Cor pulmonale acute	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Pericarditis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Pulseless electrical activity	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Sinus arrhythmia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Sinus bradycardia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Sinus node dysfunction	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Tricuspid valve incompetence	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Tricuspid valve stenosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Ventricular extrasystoles	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Cardiac disorders Ventricular tachycardia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Congenital, familial and genetic disorders Atrial septal defect	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Ear and labyrinth disorders Tinnitus	1.9% 9/470 • Number of events 9 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Ear and labyrinth disorders Vertigo	1.9% 9/470 • Number of events 9 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Ear and labyrinth disorders Deafness	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Ear and labyrinth disorders Ear congestion	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Ear and labyrinth disorders Ear haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Ear and labyrinth disorders Ear pain	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Ear and labyrinth disorders Hypoacusis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Ear and labyrinth disorders Meniere's disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Ear and labyrinth disorders Middle ear inflammation	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Ear and labyrinth disorders Vertigo positional	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Endocrine disorders Hypothyroidism	3.8% 18/470 • Number of events 18 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Endocrine disorders Hyperthyroidism	2.8% 13/470 • Number of events 15 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Endocrine disorders Adrenocortical insufficiency acute	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Endocrine disorders Cushingoid	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Eyelid oedema	1.5% 7/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Conjunctival hyperaemia	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Vision blurred	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Visual impairment	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Cataract	0.64% 3/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Amaurosis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Dry eye	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Eye pruritus	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Blepharitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Conjunctival haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Conjunctivitis allergic	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Corneal bleeding	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Corneal erosion	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Diplopia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Endocrine ophthalmopathy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Exophthalmos	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Eye discharge	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Eye haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Eye pain	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Keratitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Lacrimation increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Macular degeneration	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Ocular hyperaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Periorbital oedema	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Periorbital pain	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Photophobia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Pterygium	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Retinal haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Scleritis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Ulcerative keratitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Eye disorders Vitreous floaters	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Diarrhoea	66.2% 311/470 • Number of events 354 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Nausea	40.0% 188/470 • Number of events 197 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Vomiting	31.3% 147/470 • Number of events 161 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Abdominal pain	8.5% 40/470 • Number of events 43 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Abdominal pain upper	8.1% 38/470 • Number of events 40 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastrooesophageal reflux disease	7.7% 36/470 • Number of events 37 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Abdominal distension	7.4% 35/470 • Number of events 38 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Abdominal discomfort	6.4% 30/470 • Number of events 30 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Dyspepsia	6.0% 28/470 • Number of events 30 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Colitis	5.3% 25/470 • Number of events 29 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Constipation	4.7% 22/470 • Number of events 23 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastritis	4.7% 22/470 • Number of events 23 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Ascites	3.0% 14/470 • Number of events 14 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Dry mouth	2.1% 10/470 • Number of events 10 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Haemorrhoids	2.1% 10/470 • Number of events 10 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Irritable bowel syndrome	1.9% 9/470 • Number of events 9 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Toothache	1.9% 9/470 • Number of events 10 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Frequent bowel movements	1.7% 8/470 • Number of events 8 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Dysphagia	1.5% 7/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Diverticulum	1.3% 6/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Flatulence	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Haematemesis	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Melaena	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Abdominal pain lower	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gingival bleeding	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Haematochezia	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Hiatus hernia	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Oesophagitis	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Chronic gastritis	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Epigastric discomfort	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastric polyps	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Large intestine polyp	0.64% 3/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Mouth ulceration	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Portal hypertensive gastropathy	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.64% 3/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Anal incontinence	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Dental caries	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Enteritis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Faeces soft	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Food poisoning	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Functional gastrointestinal disorder	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Ileus	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Inguinal hernia	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Rectal haemorrhage	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Acute abdomen	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Appendicitis noninfective	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Defaecation urgency	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Eructation	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastric antral vascular ectasia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastric disorder	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastric mucosal lesion	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastric varices haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastritis erosive	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastritis haemorrhagic	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastrointestinal disorder	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastrointestinal motility disorder	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastrointestinal polyp haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastrointestinal sounds abnormal	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gastrointestinal vascular malformation haemorrhagic	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Gingival swelling	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Glossodynia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Hypoaesthesia oral	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Intestinal obstruction	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Mechanical ileus	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Mouth haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Pancreatic cyst	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Peptic ulcer	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Periodontal disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Reflux gastritis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Retching	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Salivary hypersecretion	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Gastrointestinal disorders Umbilical hernia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Oedema peripheral	18.1% 85/470 • Number of events 98 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Fatigue	13.6% 64/470 • Number of events 68 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Chest pain	9.6% 45/470 • Number of events 54 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Chest discomfort	9.4% 44/470 • Number of events 48 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Asthenia	7.2% 34/470 • Number of events 38 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Pyrexia	5.1% 24/470 • Number of events 24 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Oedema	4.7% 22/470 • Number of events 23 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Pain	3.6% 17/470 • Number of events 17 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Malaise	1.9% 9/470 • Number of events 9 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Chills	1.3% 6/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Face oedema	1.3% 6/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Disease progression	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Feeling hot	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Peripheral swelling	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Effusion	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Exercise tolerance decreased	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Feeling cold	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Multiple organ dysfunction syndrome	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Non-cardiac chest pain	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Calcinosis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Generalised oedema	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Sudden death	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Swelling	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Swelling face	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Adverse drug reaction	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Axillary pain	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Early satiety	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Hypothermia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Inflammation	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Influenza like illness	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Injection site pain	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Polyp	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Sudden cardiac death	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
General disorders Ulcer	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hepatic function abnormal	3.0% 14/470 • Number of events 15 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Cholelithiasis	1.3% 6/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Cholecystitis acute	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hepatic cirrhosis	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hepatic steatosis	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Cholecystitis chronic	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Congestive hepatopathy	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hepatic failure	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hyperbilirubinaemia	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Cholestasis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hepatic cyst	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hepatic mass	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Acute hepatic failure	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Bile duct stone	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Biliary tract disorder	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Cholecystitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hepatic calcification	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hepatitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Hepatomegaly	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Liver injury	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Nonalcoholic fatty liver disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Portal hypertension	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Portal vein thrombosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Steatohepatitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Hepatobiliary disorders Subcapsular hepatic haematoma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Immune system disorders Hypersensitivity	1.1% 5/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Immune system disorders Seasonal allergy	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Immune system disorders Atopy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Immune system disorders Drug hypersensitivity	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Immune system disorders Immune system disorder	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Upper respiratory tract infection	24.7% 116/470 • Number of events 160 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Nasopharyngitis	13.0% 61/470 • Number of events 85 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Pneumonia	10.6% 50/470 • Number of events 59 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Bronchitis	6.6% 31/470 • Number of events 41 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Urinary tract infection	6.4% 30/470 • Number of events 37 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Gastroenteritis	4.3% 20/470 • Number of events 23 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Pharyngitis	4.0% 19/470 • Number of events 27 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Respiratory tract infection	3.6% 17/470 • Number of events 23 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Influenza	3.4% 16/470 • Number of events 18 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Sinusitis	3.0% 14/470 • Number of events 17 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations COVID-19	2.6% 12/470 • Number of events 12 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Cellulitis	1.9% 9/470 • Number of events 9 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Rhinitis	1.9% 9/470 • Number of events 9 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Septic shock	1.9% 9/470 • Number of events 9 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Lower respiratory tract infection	1.5% 7/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Vaginal infection	1.5% 7/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Herpes zoster	1.3% 6/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Gastrointestinal infection	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Pharyngitis bacterial	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Sepsis	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Appendicitis	0.85% 4/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Cystitis	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Gingivitis	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations COVID-19 pneumonia	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Laryngitis	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Tonsillitis	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Clostridium difficile colitis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Clostridium difficile infection	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Conjunctivitis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Helicobacter infection	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Herpes simplex	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Localised infection	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Oral candidiasis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Otitis media	0.43% 2/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Pericoronitis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Peritonitis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Pharyngitis streptococcal	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Tooth abscess	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Urinary tract infection bacterial	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Viral upper respiratory tract infection	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Bacteraemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Bacterial translocation	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Bed bug infestation	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Body tinea	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Bronchiolitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Campylobacter infection	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Candida infection	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Cat scratch disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Cholecystitis infective	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Chronic sinusitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Conjunctivitis bacterial	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Diarrhoea infectious	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Diverticulitis	0.21% 1/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Ear infection	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Enteritis infectious	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Erysipelas	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Eye infection	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Folliculitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Gangrene	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Gastroenteritis bacterial	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Gastroenteritis viral	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Hepatitis A	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Hepatitis B	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Hepatitis C	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Hordeolum	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Impetigo	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Infected cyst	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Infected skin ulcer	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Infective exacerbation of bronchiectasis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Lymphadenitis bacterial	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Meningitis listeria	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Metapneumovirus infection	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Onychomycosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Ophthalmic herpes zoster	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Pelvic inflammatory disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Periodontitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Pharyngotonsillitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Pneumonia influenzal	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Postoperative wound infection	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Pulpitis dental	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Pyelonephritis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Sialoadenitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Sinusitis bacterial	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Skin infection	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Staphylococcal infection	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Staphylococcal sepsis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Tonsillitis bacterial	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Tooth infection	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Urethritis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Urosepsis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Infections and infestations Viral pharyngitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Ligament sprain	2.3% 11/470 • Number of events 11 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Contusion	1.9% 9/470 • Number of events 10 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Fall	1.1% 5/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Hand fracture	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Skin laceration	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Tooth fracture	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Animal bite	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Foot fracture	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Joint injury	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Skin injury	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Soft tissue injury	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Spinal fracture	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Upper limb fracture	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Wound	0.43% 2/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Accidental overdose	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Arteriovenous fistula site haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Bone contusion	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Buttock injury	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Concussion	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Face injury	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Injury	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Intentional overdose	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Joint dislocation	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Pelvic fracture	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Radius fracture	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Road traffic accident	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Spinal column injury	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Splenic rupture	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Subdural haematoma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Sunburn	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Thermal burn	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Vascular pseudoaneurysm	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Wound complication	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Injury, poisoning and procedural complications Wrist fracture	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Weight decreased	5.3% 25/470 • Number of events 25 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations N-terminal prohormone brain natriuretic peptide increased	3.2% 15/470 • Number of events 15 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood creatinine increased	2.1% 10/470 • Number of events 10 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Platelet count decreased	2.1% 10/470 • Number of events 10 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Weight increased	1.9% 9/470 • Number of events 9 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Alanine aminotransferase increased	1.7% 8/470 • Number of events 8 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood bilirubin increased	1.7% 8/470 • Number of events 8 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Oxygen saturation decreased	1.7% 8/470 • Number of events 8 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Aspartate aminotransferase increased	1.5% 7/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Gamma-glutamyltransferase increased	1.5% 7/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Haemoglobin decreased	1.5% 7/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood potassium decreased	1.3% 6/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Hepatic enzyme increased	1.3% 6/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations International normalised ratio increased	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood urea increased	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Brain natriuretic peptide increased	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood uric acid increased	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Electrocardiogram QT prolonged	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations White blood cell count decreased	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood alkaline phosphatase increased	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Catheterisation cardiac	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Haemoglobin increased	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Heart rate increased	0.43% 2/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Protein urine	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Protein urine present	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Vitamin D decreased	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Anticoagulation drug level above therapeutic	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood albumin increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood bicarbonate decreased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood bilirubin unconjugated increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood immunoglobulin G increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood pressure decreased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood pressure increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood thyroid stimulating hormone decreased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood thyroid stimulating hormone increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood triglycerides increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Blood urine	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations C-reactive protein increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Cardiac output increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Coagulation time prolonged	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Ejection fraction decreased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Electrocardiogram P wave abnormal	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Electrocardiogram ST-T change	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Electrocardiogram abnormal	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Fibrin D dimer increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Haematocrit decreased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Heart rate decreased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Heart sounds abnormal	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Liver function test abnormal	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Lymphocyte morphology abnormal	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Myocardial necrosis marker increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Occult blood	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Platelet count increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations QRS axis abnormal	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Red blood cells urine	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Serum ferritin decreased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Thyroxine free decreased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Transaminases increased	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Troponin T increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Urine output decreased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations Vitamin B12 decreased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Investigations White blood cell count increased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hypokalaemia	10.6% 50/470 • Number of events 56 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Decreased appetite	8.7% 41/470 • Number of events 43 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hyperuricaemia	3.6% 17/470 • Number of events 17 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Gout	3.2% 15/470 • Number of events 15 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Iron deficiency	2.6% 12/470 • Number of events 13 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Fluid retention	2.3% 11/470 • Number of events 12 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hyponatraemia	1.5% 7/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Dehydration	1.1% 5/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Dyslipidaemia	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Electrolyte imbalance	1.1% 5/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Fluid overload	0.85% 4/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hyperlipidaemia	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Diabetes mellitus	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Folate deficiency	0.64% 3/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hypocalcaemia	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Overweight	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Cachexia	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hyperkalaemia	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hypomagnesaemia	0.43% 2/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hypoproteinaemia	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Insulin resistance	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Malnutrition	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Metabolic acidosis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Obesity	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Vitamin D deficiency	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Calciphylaxis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Fructose intolerance	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hypercalcaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hypercholesterolaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hyperglycaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hypernatraemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hypertriglyceridaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hypervolaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hypoalbuminaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hypoglycaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Hypovolaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Lactose intolerance	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Metabolic alkalosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Steroid diabetes	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Metabolism and nutrition disorders Vitamin B complex deficiency	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Pain in jaw	21.9% 103/470 • Number of events 106 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Myalgia	16.6% 78/470 • Number of events 82 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Pain in extremity	16.6% 78/470 • Number of events 90 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Arthralgia	12.1% 57/470 • Number of events 69 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Back pain	8.7% 41/470 • Number of events 45 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Muscle spasms	1.5% 7/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Neck pain	1.5% 7/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Arthritis	1.1% 5/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Bone pain	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Muscular weakness	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	1.1% 5/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Tendonitis	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Joint swelling	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Limb discomfort	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Osteoporosis	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Costochondritis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Flank pain	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Mixed connective tissue disease	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Muscle contracture	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Muscle tightness	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Muscle twitching	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Sjogren's syndrome	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Ankylosing spondylitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Clubbing	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Enthesopathy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Exostosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Fracture malunion	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Groin pain	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Joint effusion	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Muscle atrophy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Myopathy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Osteopenia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Periarthritis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Psoriatic arthropathy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Synovial cyst	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Trigger finger	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Musculoskeletal and connective tissue disorders Undifferentiated connective tissue disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.43% 2/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of liver	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acrochordon	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of thyroid gland	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma recurrent	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer recurrent	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.21% 1/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung carcinoma cell type unspecified recurrent	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelofibrosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neurofibroma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian adenoma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) POEMS syndrome	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Teratoma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Headache	69.8% 328/470 • Number of events 348 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Dizziness	25.5% 120/470 • Number of events 131 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Syncope	3.8% 18/470 • Number of events 19 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Hypoaesthesia	3.0% 14/470 • Number of events 15 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Paraesthesia	2.3% 11/470 • Number of events 12 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Presyncope	2.3% 11/470 • Number of events 11 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Somnolence	1.3% 6/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Head discomfort	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Memory impairment	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Restless legs syndrome	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Amnesia	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Migraine	0.64% 3/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Cerebrovascular accident	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Neuralgia	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Neuropathy peripheral	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Sciatica	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Tremor	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Aphasia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Brain injury	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Coma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Disturbance in attention	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Dizziness exertional	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Dizziness postural	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Facial paralysis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Hand-arm vibration syndrome	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Hepatic encephalopathy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Hyperaesthesia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Intention tremor	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Ischaemic stroke	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Loss of consciousness	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Mental impairment	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Metabolic encephalopathy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Muscle contractions involuntary	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Nerve compression	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Post herpetic neuralgia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Sedation	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Seizure	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Spinal cord compression	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Nervous system disorders Vocal cord paralysis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Insomnia	8.5% 40/470 • Number of events 41 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Depression	4.7% 22/470 • Number of events 22 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Anxiety	2.1% 10/470 • Number of events 10 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Poor quality sleep	1.7% 8/470 • Number of events 8 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Sleep disorder	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Agitation	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Confusional state	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Restlessness	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Alcoholism	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Anxiety disorder	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Bipolar II disorder	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Borderline personality disorder	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Delirium	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Emotional distress	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Major depression	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Mental status changes	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Neurosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Panic attack	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Psychiatric disorders Stress	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Acute kidney injury	3.0% 14/470 • Number of events 16 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Proteinuria	2.6% 12/470 • Number of events 12 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Renal failure	2.1% 10/470 • Number of events 10 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Haematuria	1.3% 6/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Chronic kidney disease	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Nephrolithiasis	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Dysuria	0.64% 3/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Renal impairment	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Diabetic nephropathy	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Lupus nephritis	0.43% 2/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Oliguria	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Pollakiuria	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Bladder spasm	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Focal segmental glomerulosclerosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Glomerulonephritis acute	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Hydronephrosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Micturition urgency	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Nephropathy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Nephrotic syndrome	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Renal cyst	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Renal pain	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Renal vasculitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Scleroderma renal crisis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Tubulointerstitial nephritis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Urinary bladder polyp	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Urinary incontinence	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Urinary tract pain	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Urine abnormality	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Renal and urinary disorders Urine flow decreased	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Menstrual disorder	1.7% 8/470 • Number of events 8 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Menstruation irregular	1.3% 6/470 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Breast mass	0.85% 4/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Ovarian cyst	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Pelvic fluid collection	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Breast pain	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Fibrocystic breast disease	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Heavy menstrual bleeding	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Adnexa uteri mass	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Amenorrhoea	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Breast calcifications	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Breast cyst	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Breast hyperplasia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Breast swelling	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Dysmenorrhoea	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Gynaecomastia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Haemorrhagic ovarian cyst	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Hypomenorrhoea	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Intermenstrual bleeding	0.21% 1/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Nipple pain	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Pelvic pain	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Polycystic ovaries	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Prostatic calcification	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Prostatomegaly	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Reproductive system and breast disorders Vaginal haemorrhage	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea	24.0% 113/470 • Number of events 131 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	21.9% 103/470 • Number of events 147 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Cough	15.3% 72/470 • Number of events 76 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.1% 24/470 • Number of events 26 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Nasal congestion	4.0% 19/470 • Number of events 19 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.6% 17/470 • Number of events 17 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.6% 17/470 • Number of events 20 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Haemoptysis	3.4% 16/470 • Number of events 17 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Productive cough	3.2% 15/470 • Number of events 16 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	2.1% 10/470 • Number of events 10 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.9% 9/470 • Number of events 10 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	1.9% 9/470 • Number of events 9 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.7% 8/470 • Number of events 8 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Asthma	1.3% 6/470 • Number of events 10 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Dysphonia	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Nasal obstruction	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea paroxysmal nocturnal	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Orthopnoea	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	0.64% 3/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Wheezing	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Bronchial hyperreactivity	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Emphysema	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Choking	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea at rest	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Hiccups	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Increased upper airway secretion	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Nasal turbinate hypertrophy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Oropharyngeal discomfort	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Paranasal sinus discomfort	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Pharyngeal cyst	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Respiratory symptom	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Ventilation perfusion mismatch	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Respiratory, thoracic and mediastinal disorders Vocal cord dysfunction	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Rash	4.3% 20/470 • Number of events 20 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Pruritus	2.8% 13/470 • Number of events 13 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Erythema	2.6% 12/470 • Number of events 13 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Alopecia	2.3% 11/470 • Number of events 11 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Urticaria	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Ecchymosis	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Eczema	0.85% 4/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Skin lesion	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Acne	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Dermatitis	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Dry skin	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Skin ulcer	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Actinic keratosis	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Dermatitis contact	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Night sweats	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Rash pruritic	0.43% 2/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Alopecia areata	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Angioedema	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Blister	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Chloasma	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Cold sweat	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Dermal cyst	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Dermatitis atopic	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Dermatomyositis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Dermatosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Drug eruption	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Hyperkeratosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Intertrigo	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Lichen planus	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Nail discolouration	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Pigmentation disorder	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Pityriasis rosea	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Psoriasis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Purpura	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Rosacea	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Skin discolouration	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Skin fissures	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Skin mass	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Skin and subcutaneous tissue disorders Stasis dermatitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Social circumstances Cardiac assistance device user	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Surgical and medical procedures Tooth extraction	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Surgical and medical procedures Abortion induced	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Surgical and medical procedures Abdominal hernia repair	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Surgical and medical procedures Dacryocystorhinostomy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Surgical and medical procedures Endodontic procedure	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Surgical and medical procedures Hernia repair	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Surgical and medical procedures Knee arthroplasty	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Surgical and medical procedures Oxygen therapy	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Flushing	42.8% 201/470 • Number of events 204 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Hypotension	7.7% 36/470 • Number of events 42 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Hypertension	2.6% 12/470 • Number of events 12 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Hyperaemia	1.7% 8/470 • Number of events 8 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Haematoma	1.5% 7/470 • Number of events 8 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Hot flush	1.3% 6/470 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Peripheral venous disease	1.1% 5/470 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Cyanosis	0.85% 4/470 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Shock	0.64% 3/470 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Raynaud's phenomenon	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Varicose vein	0.43% 2/470 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Angiodysplasia	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Aortic stenosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Claudication of jaw muscles	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Orthostatic hypotension	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Pallor	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Peripheral arterial occlusive disease	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Peripheral coldness	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Phlebitis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Thrombophlebitis superficial	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.
Vascular disorders Vena cava thrombosis	0.21% 1/470 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 30 days following the final study visit (up to 356 weeks). All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit.

Additional Information

Global Medical Information

United Therapeutics Corp.

Phone: 919-485-8350

Email: clinicaltrials@unither.com

Results disclosure agreements

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

Restriction type: LTE60