Trial Outcomes & Findings for A Study of Niraparib in Patients With Ovarian Cancer Who Have Received Three or Four Previous Chemotherapy Regimens (NCT NCT02354586)

NCT ID: NCT02354586

Last Updated: 2022-09-15

Results Overview

The ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) (version1.1), where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeters (mm) in the short axis, PR=At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Primary Analysis Population comprised of participants who received 3 or 4 prior lines of therapy (LOT), had homologous recombination deficiency positive (HRDpos) tumors, had platinum-sensitive disease, and were poly(adenosine 5'-diphosphate \[ADP\]-ribose) polymerase inhibitors (PARPi) naïve.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 463 participants
• Primary outcome timeframe: Up to 3 years
• Results posted on: 2022-09-15

Participant Flow

This was an open-label, single arm study to evaluate the safety and efficacy of niraparib in ovarian cancer participants who have received previous chemotherapy regimens.

A total of 463 participants were enrolled in the study (Safety Population was comprised of all participants who received at least 1 dose of study drug).

Participant milestones

Measure	Niraparib 300 mg Participants received Niraparib (300 milligram \[mg\], taken as 3 capsules of 100 mg once daily \[QD\]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Overall Study STARTED	463
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	463

Reasons for withdrawal

Measure	Niraparib 300 mg Participants received Niraparib (300 milligram \[mg\], taken as 3 capsules of 100 mg once daily \[QD\]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Overall Study Death	230
Overall Study Withdrawal by Subject	59
Overall Study Lost to Follow-up	11
Overall Study Sponsor decision	51
Overall Study Site closure	2
Overall Study Intercurrent illness	1
Overall Study Protocol Violation	3
Overall Study Physician Decision	13
Overall Study Lack of Efficacy	86
Overall Study Adverse Event	7

Baseline Characteristics

A Study of Niraparib in Patients With Ovarian Cancer Who Have Received Three or Four Previous Chemotherapy Regimens

Baseline characteristics by cohort

Measure	Niraparib 300 mg n=463 Participants Participants received Niraparib (300 milligram \[mg\], taken as 3 capsules of 100 mg once daily \[QD\]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Age, Continuous	64.3 Years STANDARD_DEVIATION 9.28 • n=5 Participants
Sex: Female, Male Female	463 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized White	394 Participants n=5 Participants
Race/Ethnicity, Customized Black	20 Participants n=5 Participants
Race/Ethnicity, Customized Asian	16 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	32 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 3 years

Population: Primary Analysis Population. Only those participants with data available at the specified time points were analyzed.

The ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) (version1.1), where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeters (mm) in the short axis, PR=At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Primary Analysis Population comprised of participants who received 3 or 4 prior lines of therapy (LOT), had homologous recombination deficiency positive (HRDpos) tumors, had platinum-sensitive disease, and were poly(adenosine 5'-diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) naïve.

Outcome measures

Measure	Niraparib 300 mg n=47 Participants Participants received Niraparib (300 milligram \[mg\], taken as 3 capsules of 100 mg once daily \[QD\]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Objective Response Rate (ORR)	27.66 Percentage of participants Interval 15.6 to 42.6

SECONDARY outcome

Timeframe: Up to 3 years

Population: Intent-to-Treat (ITT) Population was comprised of all dosed participants with measurable disease at Baseline. Measurable disease at Baseline was determined by the existence of at least 1 target lesion at Baseline tumor scan based on investigator's assessment. Only those participants with data available at the specified time points were analyzed.

DoR was defined as the time from first documentation of CR or PR until the time of first documentation of disease progression (PD) as assessed by the Investigator per RECIST (version1.1). DoR was analyzed using Kaplan-Meier (KM) method.

Outcome measures

Measure	Niraparib 300 mg n=39 Participants Participants received Niraparib (300 milligram \[mg\], taken as 3 capsules of 100 mg once daily \[QD\]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Duration of Response (DoR)	9.4 Months Interval 6.6 to 18.3

SECONDARY outcome

Timeframe: Up to 3 years

Population: ITT Population. All the participants from the ITT Population were analyzed (461 participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

The ORR was defined as the percentage of participants achieving CR or PR as assessed by the Investigator per RECIST (version1.1), where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. ORR was evaluated for participants with following characteristics: HRD status (positive, negative and unknown) and BRCA status (mutation positive, wild-type and unknown).

Outcome measures

Measure	Niraparib 300 mg n=461 Participants Participants received Niraparib (300 milligram \[mg\], taken as 3 capsules of 100 mg once daily \[QD\]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
ORR by HRD Status and Breast Cancer Gene (BRCA) Status HRD positive, n=221	14.0 Percentage of participants Interval 9.7 to 19.3
ORR by HRD Status and Breast Cancer Gene (BRCA) Status HRD negative, n=195	2.6 Percentage of participants Interval 0.8 to 5.9
ORR by HRD Status and Breast Cancer Gene (BRCA) Status HRD unknown, n=45	6.7 Percentage of participants Interval 1.4 to 18.3
ORR by HRD Status and Breast Cancer Gene (BRCA) Status BRCA mutation positive, n=87	23.0 Percentage of participants Interval 14.6 to 33.2
ORR by HRD Status and Breast Cancer Gene (BRCA) Status BRCA wild-type, n=317	5.0 Percentage of participants Interval 2.9 to 8.1
ORR by HRD Status and Breast Cancer Gene (BRCA) Status BRCA unknown, n=57	5.3 Percentage of participants Interval 1.1 to 14.6

SECONDARY outcome

Timeframe: Up to 3 years

Population: ITT Population. Only those participants with data available at the specified time points were analyzed.

Disease control rate was defined as the percentage of participants achieving CR, PR, or stable disease (SD) as assessed by the Investigator per RECIST (version1.1). The exact (Clopper-Pearson) method was used to calculate 95% confidence interval.

Outcome measures

Measure	Niraparib 300 mg n=461 Participants Participants received Niraparib (300 milligram \[mg\], taken as 3 capsules of 100 mg once daily \[QD\]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Disease Control Rate (DCR)	49.02 Percentage of participants Interval 44.4 to 53.7

SECONDARY outcome

Timeframe: Up to 3 years

Population: ITT Population. Only those participants with data available at the specified time points were analyzed.

Progression-free survival was defined as the time from the date of first dose to the earlier date of assessment of progression or death by any cause in the absence of progression as assessed by the Investigator per RECIST (version 1.1) or clinical criteria. Progression is defined using RECIST version1.1 as at least a 20% increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions.

Outcome measures

Measure	Niraparib 300 mg n=461 Participants Participants received Niraparib (300 milligram \[mg\], taken as 3 capsules of 100 mg once daily \[QD\]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Progression Free Survival	3.5 Months Interval 3.2 to 3.7

SECONDARY outcome

Timeframe: Up to 3 years

Population: ITT Population. Only those participants with data available at the specified time points were analyzed.

Overall Survival was defined as the time from the date of the first dose to the date of death by any cause. It was calculated as (Date of Death minus First dose date plus 1) divided by 30.4375.

Outcome measures

Measure	Niraparib 300 mg n=461 Participants Participants received Niraparib (300 milligram \[mg\], taken as 3 capsules of 100 mg once daily \[QD\]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Overall Survival	17.2 Months Interval 14.9 to 19.8

SECONDARY outcome

Timeframe: Up to 3 years

Population: ITT Population. Only those participants with data available at the specified time points were analyzed.

Time to first subsequent therapy (TFST) was defined as the time from the date of first dose to the date of first subsequent therapy or death, whichever occurs first. It was calculated as (Earlier of [First dose of first subsequent therapy or death] minus First dose date plus 1) divided by 30.4375.

Outcome measures

Measure	Niraparib 300 mg n=461 Participants Participants received Niraparib (300 milligram \[mg\], taken as 3 capsules of 100 mg once daily \[QD\]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Time to First Subsequent Therapy (TFST)	6.8 Months Interval 5.9 to 7.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to a maximum of 71.56 months

Population: Safety Population was comprised of all participants who received at least 1 dose of study drug.

An adverse event is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE. Adverse events which were not serious were considered as Non-serious adverse events.

Outcome measures

Measure	Niraparib 300 mg n=463 Participants Participants received Niraparib (300 milligram \[mg\], taken as 3 capsules of 100 mg once daily \[QD\]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Number of Participants With Any Non-serious Adverse Event (Non-SAE) and Any Serious Adverse Event (SAE) Any non-SAE	461 Participants
Number of Participants With Any Non-serious Adverse Event (Non-SAE) and Any Serious Adverse Event (SAE) Any SAE	200 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years

Population: Safety Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.

Number of participants with abnormality in hematology parameters were planned to be analyzed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years

Population: Safety Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.

Number of participants with abnormality in clinical chemistry parameters were planned to be analyzed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years

Population: Safety Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.

Number of participants with abnormality in vital signs were planned to be analyzed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years

Population: Safety Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.

Number of participants with abnormality in physical examination were planned to be analyzed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years

Population: Safety Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.

Number of participants who were administered concomitant medications were planned to be analyzed.

Outcome measures

Outcome data not reported

Adverse Events

Niraparib 300 mg

Serious events: 200 serious events

Other events: 461 other events

Deaths: 232 deaths

Serious adverse events

Measure	Niraparib 300 mg n=463 participants at risk Participants received Niraparib (300 milligram \[mg\], taken as 3 capsules of 100 mg once daily \[QD\]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Blood and lymphatic system disorders Anaemia	3.2% 15/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Bone marrow failure	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Leukopenia	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Lymphopenia	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Neutropenia	2.4% 11/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Normochromic anaemia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Pancytopenia	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	7.3% 34/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Arrhythmia supraventricular	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Atrial fibrillation	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac arrest	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Cardiopulmonary failure	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Myocardial infarction	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Palpitations	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Pericardial effusion	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Supraventricular tachycardia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Tachycardia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Retinal tear	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Vitreous haemorrhage	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal discomfort	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal distension	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain	3.7% 17/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Ascites	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Colitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	2.2% 10/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dysphagia	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Enteritis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Erosive oesophagitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastric haemorrhage	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastritis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastrointestinal fistula	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Ileus	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Intestinal obstruction	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Intestinal perforation	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Large intestinal obstruction	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	4.5% 21/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Obstruction gastric	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Oesophageal varices haemorrhage	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Oesophagitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Rectal haemorrhage	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Small intestinal obstruction	7.3% 34/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Stomatitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	5.8% 27/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Asthenia	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Chest pain	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Fatigue	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Mucosal inflammation	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Pyrexia	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Strangulated hernia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Sudden death	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Acute hepatic failure	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Biliary tract disorder	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholangitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Hepatic failure	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Hyperbilirubinaemia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Bacteraemia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Bronchitis	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Escherichia urinary tract infection	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis viral	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Influenza	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Joint abscess	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Liver abscess	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Osteomyelitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Pharyngitis streptococcal	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Pyelonephritis	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Sepsis	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Streptococcal bacteraemia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Wound infection	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Gastrointestinal stoma complication	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Overdose	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Subdural haematoma	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood creatinine increased	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Electrocardiogram QT prolonged	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Gamma-glutamyltransferase increased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Haemoglobin decreased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Neutrophil count decreased	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Platelet count decreased	1.5% 7/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Dehydration	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Electrolyte imbalance	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypocalcaemia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypophagia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Flank pain	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer recurrent	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Headache	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Seizure	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Status epilepticus	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Transient global amnesia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Transient ischaemic attack	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Psychiatric disorders Mental status changes	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Psychiatric disorders Suicidal ideation	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Acute kidney injury	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Haematuria	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Hydronephrosis	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Nephrolithiasis	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Ureteric obstruction	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Urinary tract obstruction	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Deep vein thrombosis	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Embolism	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Hypertension	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Hypotension	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Mallory-Weiss syndrome	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.

Other adverse events

Measure	Niraparib 300 mg n=463 participants at risk Participants received Niraparib (300 milligram \[mg\], taken as 3 capsules of 100 mg once daily \[QD\]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Blood and lymphatic system disorders Anaemia	50.3% 233/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Anaemia macrocytic	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Aplastic anaemia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Increased tendency to bruise	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Leukocytosis	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Leukopenia	6.7% 31/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Lymph node pain	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Lymphadenopathy	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Lymphocytosis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Lymphopenia	3.2% 15/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Neutropenia	11.2% 52/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Neutrophilia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Pancytopenia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	32.6% 151/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Thrombocytosis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Angina pectoris	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Atrial fibrillation	1.1% 5/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Atrial flutter	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Atrioventricular block first degree	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Extrasystoles	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Left atrial enlargement	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Myocardial infarction	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Palpitations	7.3% 34/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Pericardial effusion	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Sinus tachycardia	3.0% 14/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Tachycardia	3.2% 15/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Ventricular arrhythmia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Ventricular extrasystoles	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Auditory disorder	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Ear congestion	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Ear discomfort	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Ear pain	1.1% 5/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Middle ear inflammation	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Tinnitus	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Vertigo	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Vestibular disorder	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Endocrine disorders Hyperthyroidism	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Endocrine disorders Hypothyroidism	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Abnormal sensation in eye	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Age-related macular degeneration	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Asthenopia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Cataract	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Corneal disorder	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Diplopia	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Dry eye	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Eye disorder	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Lacrimation increased	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Night blindness	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Ocular hyperaemia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Photophobia	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Photopsia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Vision blurred	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Visual impairment	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Vitreous floaters	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal discomfort	2.2% 10/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal distension	14.7% 68/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal hernia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain	19.2% 89/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain lower	2.4% 11/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain upper	6.0% 28/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Anal fissure	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Anal haemorrhage	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Anal incontinence	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Anorectal discomfort	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Aphthous ulcer	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Ascites	3.0% 14/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Colitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	34.8% 161/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Defaecation urgency	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dental caries	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	17.5% 81/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dry mouth	5.2% 24/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dyschezia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dyspepsia	7.3% 34/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dysphagia	1.5% 7/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Epigastric discomfort	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Erosive oesophagitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Eructation	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Faeces discoloured	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Faeces hard	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Faeces soft	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Flatulence	3.5% 16/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastric varices	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastrointestinal pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.6% 26/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gingival bleeding	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Haematemesis	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Haematochezia	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Haemorrhoids	1.1% 5/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Hypoaesthesia oral	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Impaired gastric emptying	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Intestinal obstruction	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Large intestinal obstruction	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Lip oedema	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Mouth haemorrhage	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Mouth swelling	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	67.0% 310/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Obstruction gastric	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Odynophagia	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Oesophageal pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Oesophagitis	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Oral mucosal erythema	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Oral pain	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Paraesthesia oral	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Proctalgia	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Rectal haemorrhage	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Rectal obstruction	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Rectal spasm	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Retching	1.5% 7/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Salivary hypersecretion	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Small intestinal obstruction	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Stomatitis	8.2% 38/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Swollen tongue	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Tongue disorder	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Toothache	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	43.6% 202/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Asthenia	6.5% 30/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Axillary pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Chest discomfort	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Chest pain	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Chills	2.8% 13/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Drug withdrawal syndrome	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Early satiety	2.2% 10/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Energy increased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Face oedema	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Facial pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Fatigue	52.7% 244/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Feeling jittery	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Gait disturbance	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Influenza like illness	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Injection site pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Localised oedema	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Malaise	1.5% 7/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Medical device pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Mucosal inflammation	2.8% 13/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Non-cardiac chest pain	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Oedema	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Oedema peripheral	6.7% 31/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Pain	2.2% 10/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Performance status decreased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Peripheral swelling	3.2% 15/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Pyrexia	4.8% 22/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Suprapubic pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Temperature intolerance	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Tenderness	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Thirst	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholecystitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholelithiasis	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Immune system disorders Drug hypersensitivity	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Immune system disorders Hypersensitivity	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Immune system disorders Seasonal allergy	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Abdominal abscess	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Bacteraemia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Beta haemolytic streptococcal infection	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Bronchitis	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Candida infection	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Cellulitis	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Chronic sinusitis	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Clostridium difficile infection	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Conjunctivitis viral	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Cystitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Ear infection	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Eye infection	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Folliculitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Gingivitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Hepatitis viral	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Herpes zoster	1.9% 9/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Infected cyst	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Influenza	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Laryngitis	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Localised infection	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Lower respiratory tract infection	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Oesophageal candidiasis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Oral candidiasis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Oral herpes	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Paronychia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Pharyngitis streptococcal	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	1.5% 7/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Pyelonephritis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Rhinitis	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Sepsis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Sinusitis	2.6% 12/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Tinea pedis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Tooth infection	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	2.8% 13/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	14.7% 68/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Viral infection	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Viral upper respiratory tract infection	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Vulvovaginal mycotic infection	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Ankle fracture	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Arthropod bite	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Contusion	3.7% 17/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Ear canal abrasion	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Facial bones fracture	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Fall	1.1% 5/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Foot fracture	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Gastrointestinal stoma complication	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Hand fracture	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Head injury	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Incisional hernia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Muscle strain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Post-traumatic pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Procedural pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Radiation skin injury	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Rib fracture	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Subarachnoid haemorrhage	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Subdural haematoma	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Sunburn	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Thermal burn	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Tooth fracture	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Upper limb fracture	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Activated partial thromboplastin time prolonged	3.7% 17/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Alanine aminotransferase increased	6.9% 32/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Amylase increased	5.6% 26/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Aspartate aminotransferase increased	9.5% 44/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Bacterial test positive	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Bilirubin conjugated increased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood albumin decreased	1.5% 7/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood alkaline phosphatase decreased	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood alkaline phosphatase increased	11.2% 52/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood bilirubin increased	2.2% 10/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood calcium decreased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood chloride decreased	1.9% 9/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood creatine increased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood creatinine decreased	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood creatinine increased	16.4% 76/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood glucose increased	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood lactate dehydrogenase increased	3.2% 15/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood lactic acid increased	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood magnesium decreased	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood potassium decreased	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood pressure increased	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood pressure orthostatic decreased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood sodium decreased	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood sodium increased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood urea decreased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood urea increased	2.4% 11/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood urine present	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Carbohydrate antigen 125 increased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Eastern Cooperative Oncology Group performance status worsened	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Electrocardiogram QT prolonged	4.5% 21/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Gamma-glutamyltransferase increased	10.8% 50/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Glomerular filtration rate abnormal	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Glomerular filtration rate decreased	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Glomerular filtration rate increased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Glucose tolerance test abnormal	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Glucose urine present	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Haemoglobin decreased	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Haemoglobin urine present	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Heart rate increased	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations International normalised ratio increased	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Lymphocyte count decreased	6.9% 32/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Lymphocyte count increased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Mean cell volume increased	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Mean platelet volume decreased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Neutrophil count decreased	8.4% 39/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Neutrophil count increased	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Nitrite urine present	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Platelet count decreased	21.8% 101/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Platelet count increased	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Protein total decreased	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Protein total increased	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Protein urine present	2.2% 10/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Prothrombin time prolonged	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations QRS axis abnormal	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Urine ketone body present	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Urine leukocyte esterase	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Urine leukocyte esterase positive	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Vitamin D decreased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Weight decreased	9.7% 45/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Weight increased	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations White blood cell count decreased	12.1% 56/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations White blood cell count increased	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations White blood cells urine positive	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Appetite disorder	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Decreased appetite	27.4% 127/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Dehydration	9.5% 44/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Electrolyte imbalance	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Gout	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypercalcaemia	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	7.3% 34/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	2.2% 10/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypermagnesaemia	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypernatraemia	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperuricaemia	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypervolaemia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	5.4% 25/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypocalcaemia	3.7% 17/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypochloraemia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	8.4% 39/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypomagnesaemia	19.7% 91/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	11.2% 52/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypophosphataemia	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypoproteinaemia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Iron deficiency	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Malnutrition	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	5.2% 24/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	10.8% 50/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Costochondritis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Flank pain	1.9% 9/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Groin pain	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Joint swelling	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	3.5% 16/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscle twitching	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscular weakness	4.1% 19/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.4% 11/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.7% 17/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	3.7% 17/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Neck pain	1.9% 9/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	3.9% 18/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in jaw	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Spondylitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Trismus	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to breast	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer metastatic	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Akathisia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Amnesia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Anosmia	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Aphasia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Ataxia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Balance disorder	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Cognitive disorder	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Coordination abnormal	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	11.2% 52/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness postural	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Dysgeusia	4.1% 19/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Extrapyramidal disorder	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Headache	19.2% 89/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Hypoaesthesia	1.5% 7/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Hypogeusia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Hyposmia	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Lethargy	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Loss of consciousness	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Loss of proprioception	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Memory impairment	1.1% 5/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Migraine	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Monoplegia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Neuralgia	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Neuropathy peripheral	3.0% 14/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Paraesthesia	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Parosmia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Peripheral sensory neuropathy	2.2% 10/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Post-traumatic headache	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Presyncope	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Restless legs syndrome	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Sciatica	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Secondary cerebellar degeneration	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Sinus headache	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Somnolence	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Syncope	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Tremor	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Vocal cord paralysis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Product Issues Device occlusion	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Psychiatric disorders Abnormal dreams	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Psychiatric disorders Anxiety	8.2% 38/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Psychiatric disorders Confusional state	2.4% 11/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Psychiatric disorders Depression	3.7% 17/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Psychiatric disorders Insomnia	22.7% 105/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Psychiatric disorders Mania	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Psychiatric disorders Mental status changes	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Psychiatric disorders Nervousness	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Psychiatric disorders Restlessness	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Psychiatric disorders Suicidal ideation	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Acute kidney injury	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Bladder discomfort	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Bladder spasm	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Chromaturia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Chronic kidney disease	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Dysuria	2.2% 10/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Glycosuria	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Haematuria	2.6% 12/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Hydronephrosis	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Incontinence	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Micturition urgency	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Pollakiuria	1.9% 9/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Proteinuria	3.2% 15/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal failure	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal impairment	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Renal pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Ureteric obstruction	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Urethral pain	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Urinary hesitation	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Urinary incontinence	1.1% 5/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Urinary retention	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Urinary tract pain	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Urine abnormality	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Urine odour abnormal	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Urogenital disorder	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Adnexa uteri pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Atrophic vulvovaginitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Breast disorder	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Breast mass	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Breast pain	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Breast swelling	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Cystocele	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Nipple pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Pelvic discomfort	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Pelvic pain	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Vaginal discharge	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Vaginal disorder	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Vaginal haemorrhage	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Vulvovaginal discomfort	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Vulvovaginal dryness	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Vulvovaginal erythema	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Vulvovaginal pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Reproductive system and breast disorders Vulvovaginal pruritus	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	13.8% 64/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dysphonia	1.1% 5/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	19.0% 88/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea at rest	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	1.9% 9/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.0% 23/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Hiccups	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	2.2% 10/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.8% 22/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Painful respiration	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.9% 18/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Productive cough	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary pain	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory depression	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Sinus disorder	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Sputum increased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Throat irritation	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Wheezing	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Acne cystic	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	3.9% 18/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Blood blister	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Cold sweat	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Dry skin	1.5% 7/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Ecchymosis	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Eczema	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Erythema	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.3% 6/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Madarosis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Nail discolouration	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Night sweats	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Onychoclasis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Pain of skin	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Petechiae	1.7% 8/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Photosensitivity reaction	1.1% 5/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	1.9% 9/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Purpura	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash	4.1% 19/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash erythematous	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash maculo-papular	1.1% 5/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash pruritic	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Skin exfoliation	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Skin lesion	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Skin mass	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Skin tightness	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Skin ulcer	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Urticaria	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Surgical and medical procedures Tooth extraction	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Angiopathy	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Deep vein thrombosis	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Embolism	0.86% 4/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Flushing	1.1% 5/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Haematoma	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Hot flush	4.5% 21/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Hypertension	13.0% 60/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Hypotension	1.1% 5/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Lymphoedema	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Orthostatic hypotension	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Peripheral coldness	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Thrombosis	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Vascular disorders Venous occlusion	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Blister	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Bundle branch block right	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Coronary artery disease	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Cardiac disorders Sinus bradycardia	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Paraesthesia ear	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Endocrine disorders Hyperparathyroidism	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Eye pruritus	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Eye disorders Scleral discolouration	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal rigidity	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastric mucosa erythema	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Large intestine polyp	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Mouth ulceration	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Oesophageal stenosis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Complication associated with device	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Cyst	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
General disorders Swelling	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Hepatobiliary disorders Jaundice	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations COVID-19	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Helicobacter infection	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	3.5% 16/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Otitis externa	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Perineal abscess	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Tooth abscess	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Infections and infestations Vulval abscess	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Procedural haemorrhage	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Skin laceration	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Blood cholesterol increased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Investigations Lipase increased	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypertriglyceridaemia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteoporosis	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to peritoneum	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Ageusia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Dyskinesia	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Head titubation	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Nervous system disorders Taste disorder	0.65% 3/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Psychiatric disorders Panic attack	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Renal and urinary disorders Ureterolithiasis	0.43% 2/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Asthma	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dry throat	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.22% 1/463 • All-cause mortality, Non-serious adverse events (Non-SAEs) and Serious adverse events (SAEs) were reported up to a maximum of 71.56 months All-cause mortality, Non-SAEs and SAEs were reported for Safety Population which comprised of all participants who received at least 1 dose of study drug.

Additional Information

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GlaxoSmithKline

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Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

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