Trial Outcomes & Findings for PORtopulmonary Hypertension Treatment wIth maCitentan - a randOmized Clinical Trial (NCT NCT02382016)

NCT ID: NCT02382016

Last Updated: 2025-03-30

Results Overview

The relative change from baseline to Week 12 in PVR is expressed as a ratio of Week 12 to baseline PVR.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 85 participants
• Primary outcome timeframe: From enrollment/baseline to Week 12 in the Double Blind (DB) treatment period
• Results posted on: 2025-03-30

Participant Flow

Participants at 39 sites in 7 countries were screened and were randomized at 36 sites in these 7 countries (Brazil, Czech Republic, France, Germany, Spain, UK and US).

A total of 119 participants were screened and 85 participants were randomized (43 to macitentan 10 mg once daily and 42 to matching placebo) and received double-blind (DB) study treatment. Overall, 80 participants who completed DB treatment period entered the open-label (OL) treatment period and 33 participants in open-label extension (OLE) period.

Participant milestones

Measure	Macitentan 10 mg Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. Participants who completed DB treatment period continued to receive macitentan 10 mg for 12 weeks (up to Week 24) in OL treatment period . Participants (who were randomized at French sites) who completed the core phase of the study as scheduled and opted to continue receiving OL study treatment continued to receive macitentan 10 mg in OLE period.	Placebo Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. Participants who completed DB treatment period were administered with macitentan 10 mg for 12 weeks (up to Week 24) in OL treatment period. Participants who were randomized at French sites who completed the core study as scheduled and opted to continue receiving OL study treatment continued to receive macitentan 10mg in OLE period.
Double-blind (DB) Treatment Period STARTED	43	42
Double-blind (DB) Treatment Period COMPLETED	39	41
Double-blind (DB) Treatment Period NOT COMPLETED	4	1
Open-label (OL) Treatment Period STARTED	80	0
Open-label (OL) Treatment Period COMPLETED	71	0
Open-label (OL) Treatment Period NOT COMPLETED	9	0
OL Extension Period STARTED	33	0
OL Extension Period COMPLETED	27	0
OL Extension Period NOT COMPLETED	6	0

Reasons for withdrawal

Measure	Macitentan 10 mg Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. Participants who completed DB treatment period continued to receive macitentan 10 mg for 12 weeks (up to Week 24) in OL treatment period . Participants (who were randomized at French sites) who completed the core phase of the study as scheduled and opted to continue receiving OL study treatment continued to receive macitentan 10 mg in OLE period.	Placebo Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. Participants who completed DB treatment period were administered with macitentan 10 mg for 12 weeks (up to Week 24) in OL treatment period. Participants who were randomized at French sites who completed the core study as scheduled and opted to continue receiving OL study treatment continued to receive macitentan 10mg in OLE period.
Double-blind (DB) Treatment Period Physician Decision	3	0
Double-blind (DB) Treatment Period Lack of Efficacy	1	0
Double-blind (DB) Treatment Period Withdrawal by Subject	0	1
Open-label (OL) Treatment Period Physician Decision	3	0
Open-label (OL) Treatment Period Withdrawal by Subject	2	0
Open-label (OL) Treatment Period Death	4	0
OL Extension Period Physician Decision	3	0
OL Extension Period Death	2	0
OL Extension Period Withdrawal by Subject	1	0

Baseline Characteristics

PORtopulmonary Hypertension Treatment wIth maCitentan - a randOmized Clinical Trial

Baseline characteristics by cohort

Measure	Macitentan 10 mg n=43 Participants Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.	Placebo n=42 Participants Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.	Total n=85 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	35 Participants n=93 Participants	29 Participants n=4 Participants	64 Participants n=27 Participants
Age, Categorical >=65 years	8 Participants n=93 Participants	13 Participants n=4 Participants	21 Participants n=27 Participants
Age, Continuous	58.0 years STANDARD_DEVIATION 8.7 • n=93 Participants	59.0 years STANDARD_DEVIATION 9.5 • n=4 Participants	58.5 years STANDARD_DEVIATION 9.1 • n=27 Participants
Sex: Female, Male Female	21 Participants n=93 Participants	20 Participants n=4 Participants	41 Participants n=27 Participants
Sex: Female, Male Male	22 Participants n=93 Participants	22 Participants n=4 Participants	44 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=93 Participants	6 Participants n=4 Participants	12 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=93 Participants	15 Participants n=4 Participants	34 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	18 Participants n=93 Participants	21 Participants n=4 Participants	39 Participants n=27 Participants
Race/Ethnicity, Customized Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized White	23 Participants n=93 Participants	21 Participants n=4 Participants	44 Participants n=27 Participants
Race/Ethnicity, Customized Other	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Not Applicable	18 Participants n=93 Participants	21 Participants n=4 Participants	39 Participants n=27 Participants
Region of Enrollment United States	12 Participants n=93 Participants	11 Participants n=4 Participants	23 Participants n=27 Participants
Region of Enrollment Brazil	2 Participants n=93 Participants	3 Participants n=4 Participants	5 Participants n=27 Participants
Region of Enrollment Czech Republic	1 Participants n=93 Participants	3 Participants n=4 Participants	4 Participants n=27 Participants
Region of Enrollment France	18 Participants n=93 Participants	21 Participants n=4 Participants	39 Participants n=27 Participants
Region of Enrollment Germany	4 Participants n=93 Participants	4 Participants n=4 Participants	8 Participants n=27 Participants
Region of Enrollment Spain	4 Participants n=93 Participants	0 Participants n=4 Participants	4 Participants n=27 Participants
Region of Enrollment United Kingdom	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Pulmonary arterial hypertension (PAH)-specific therapy Yes	27 Participants n=93 Participants	27 Participants n=4 Participants	54 Participants n=27 Participants
Pulmonary arterial hypertension (PAH)-specific therapy No	16 Participants n=93 Participants	15 Participants n=4 Participants	31 Participants n=27 Participants
Body Mass Index (BMI) at baseline	29.01 Kilogram per meter^2 (Kg/m^2) STANDARD_DEVIATION 4.79 • n=93 Participants	29.33 Kilogram per meter^2 (Kg/m^2) STANDARD_DEVIATION 4.04 • n=4 Participants	29.17 Kilogram per meter^2 (Kg/m^2) STANDARD_DEVIATION 4.41 • n=27 Participants
Time since portal hypertension diagnosis	23 Months n=93 Participants	31 Months n=4 Participants	25 Months n=27 Participants
Time since PAH diagnosis	7 Months n=93 Participants	12 Months n=4 Participants	10 Months n=27 Participants
Pulmonary vascular resistance (PVR) at baseline (calculated)	552.4 Dyn*sec/cm^5 STANDARD_DEVIATION 192.8 • n=93 Participants	521.7 Dyn*sec/cm^5 STANDARD_DEVIATION 163.3 • n=4 Participants	537.2 Dyn*sec/cm^5 STANDARD_DEVIATION 178.4 • n=27 Participants

PRIMARY outcome

Timeframe: From enrollment/baseline to Week 12 in the Double Blind (DB) treatment period

The relative change from baseline to Week 12 in PVR is expressed as a ratio of Week 12 to baseline PVR.

Outcome measures

Measure	Macitentan 10 mg n=43 Participants Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.	Placebo n=42 Participants Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.
Relative Change From Baseline to Week 12 in Pulmonary Vascular Resistance (PVR).	0.63 ratio Interval 0.58 to 0.67	0.98 ratio Interval 0.91 to 1.05

SECONDARY outcome

Timeframe: From enrollment/baseline to Week 12 in the DB treatment period

The purpose of the six minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.

Outcome measures

Measure	Macitentan 10 mg n=43 Participants Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.	Placebo n=42 Participants Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.
Change From Baseline to Week 12 in 6-minute Walk Distance (6MWD) Change of 6MWD from baseline to Week 12	6.4 meter Standard Deviation 65.74	-2.4 meter Standard Deviation 43.65
Change From Baseline to Week 12 in 6-minute Walk Distance (6MWD) 6MWD at baseline	385.8 meter Standard Deviation 99.97	383.2 meter Standard Deviation 108.90
Change From Baseline to Week 12 in 6-minute Walk Distance (6MWD) 6MWD at Week 12	392.2 meter Standard Deviation 98.46	380.8 meter Standard Deviation 114.98

SECONDARY outcome

Timeframe: From enrollment/baseline to Week 12 in the DB treatment period

Changes from baseline to Week 12 in WHO FC were dichotomized as worsening (i.e., change > 0) versus no change or improvement (i.e., change ≤ 0). Class I: no symptoms with exercise or at rest. No limitation of activity. Class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing a flight of stairs, grocery shopping, or making the bed). Class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. Class IV: symptoms at rest (e.g. dyspnea and/or fatigue) and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure.

Outcome measures

Measure	Macitentan 10 mg n=43 Participants Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.	Placebo n=42 Participants Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.
Change From Baseline to Week 12 in WHO Functional Class (FC) WHO FC IV at Week 12	0 Participants	0 Participants
Change From Baseline to Week 12 in WHO Functional Class (FC) WHO FC I at baseline	1 Participants	1 Participants
Change From Baseline to Week 12 in WHO Functional Class (FC) WHO FC II at baseline	27 Participants	23 Participants
Change From Baseline to Week 12 in WHO Functional Class (FC) WHO FC III at baseline	15 Participants	18 Participants
Change From Baseline to Week 12 in WHO Functional Class (FC) WHO FC IV at baseline	0 Participants	0 Participants
Change From Baseline to Week 12 in WHO Functional Class (FC) WHO FC I at Week 12	3 Participants	4 Participants
Change From Baseline to Week 12 in WHO Functional Class (FC) WHO FC II at Week 12	27 Participants	23 Participants
Change From Baseline to Week 12 in WHO Functional Class (FC) WHO FC III at Week 12	13 Participants	15 Participants
Change From Baseline to Week 12 in WHO Functional Class (FC) Improved from baseline to Week 12	9 Participants	7 Participants
Change From Baseline to Week 12 in WHO Functional Class (FC) Worsened from baseline to Week 12	6 Participants	1 Participants
Change From Baseline to Week 12 in WHO Functional Class (FC) Unchanged from baseline to Week 12	28 Participants	34 Participants

SECONDARY outcome

Timeframe: From enrollment/baseline to Week 12 in the DB treatment period

Population: Full Analysis Set(FAS): All randomized participants who received at least one dose of study drug in DB treatment, have baseline value for PVR, evaluated As per assigned treatment. Here, 'N'(number of participants analyzed included population included participants with available baseline data.

NT-proBNP functions as a strong indicator of prognosis in patients with pulmonary hypertension (PH). The relative change from baseline to Week 12 in NT-proBNP is expressed as a ratio of Week 12 to baseline NT-proBNP.

Outcome measures

Measure	Macitentan 10 mg n=41 Participants Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.	Placebo n=40 Participants Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.
Change From Baseline to Week 12 in the Biomarker N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)	0.86 ratio Interval 0.67 to 1.11	1.04 ratio Interval 0.81 to 1.34

SECONDARY outcome

Timeframe: From enrollment/baseline to Week 12 in the DB treatment period

Population: Full Analysis Set(FAS): All randomized participants who received at least one dose of study drug in DB treatment, have baseline value for PVR, evaluated As per assigned treatment. Here, 'N'(number of participants analyzed included population included participants with available baseline data.

mRAP is the mean blood pressure in the right atrium of the heart.

Outcome measures

Measure	Macitentan 10 mg n=42 Participants Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.	Placebo n=42 Participants Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.
Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP) mRAP at baseline	7.3 mmHg Standard Deviation 3.74	6.7 mmHg Standard Deviation 3.60
Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP) mRAP at Week 12	9.0 mmHg Standard Deviation 5.32	7.0 mmHg Standard Deviation 2.93
Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP) Change in mRAP from baseline to Week 12	1.6 mmHg Standard Deviation 5.55	0.3 mmHg Standard Deviation 3.29

SECONDARY outcome

Timeframe: From enrollment/baseline to Week 12 in the DB treatment period

mPAP is the mean blood pressure inside the pulmonary artery which moves the blood from the heart to the lungs. Monitoring of mPAP can detect small changes in the function of the heart.

Outcome measures

Measure	Macitentan 10 mg n=43 Participants Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.	Placebo n=42 Participants Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.
Change From Baseline to Week 12 in Mean Pulmonary Artery Pressure (mPAP) mPAP at baseline	46.4 mmHg Standard Deviation 7.89	43.8 mmHg Standard Deviation 8.52
Change From Baseline to Week 12 in Mean Pulmonary Artery Pressure (mPAP) mPAP at Week 12	40.0 mmHg Standard Deviation 7.61	44.2 mmHg Standard Deviation 8.26
Change From Baseline to Week 12 in Mean Pulmonary Artery Pressure (mPAP) Change in mPAP at Week 12	-6.4 mmHg Standard Deviation 4.94	0.4 mmHg Standard Deviation 7.04

SECONDARY outcome

Timeframe: From enrollment/baseline to Week 12 in the DB treatment period

The cardiac index is an assessment of the function of the heart and relates the cardiac output to the patient's body size (the patient's body surface area).

Outcome measures

Measure	Macitentan 10 mg n=43 Participants Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.	Placebo n=42 Participants Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.
Change From Baseline to Week 12 in Cardiac Index Cardiac index at baseline	3.1 L/min/m^2 Standard Deviation 0.83	2.9 L/min/m^2 Standard Deviation 0.76
Change From Baseline to Week 12 in Cardiac Index Cardiac index at Week 12	3.7 L/min/m^2 Standard Deviation 1.04	3.0 L/min/m^2 Standard Deviation 0.82
Change From Baseline to Week 12 in Cardiac Index Change in cardiac index at Week 12	0.6 L/min/m^2 Standard Deviation 0.8	0.1 L/min/m^2 Standard Deviation 0.6

SECONDARY outcome

Timeframe: From enrollment/baseline to Week 12 in the DB treatment period

TPR is the resistance the pulmonary circulation that must be overcome in order for the blood flow to occur. It takes into account the blood pressure in the pulmonary arteries and the cardiac output. It is an important measurement to monitor the function of the pulmonary circulation and detect disease progression or improvement.

Outcome measures

Measure	Macitentan 10 mg n=43 Participants Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.	Placebo n=42 Participants Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.
Change From Baseline to Week 12 in Total Pulmonary Resistance (TPR) TPR at baseline	689.3 dyn*sec/cm^5 Standard Deviation 228.59	671.5 dyn*sec/cm^5 Standard Deviation 199.73
Change From Baseline to Week 12 in Total Pulmonary Resistance (TPR) TPR at Week 12	489.4 dyn*sec/cm^5 Standard Deviation 157.13	653.1 dyn*sec/cm^5 Standard Deviation 197.88
Change From Baseline to Week 12 in Total Pulmonary Resistance (TPR) Change in TPR from baseline to Week 12	-199.8 dyn*sec/cm^5 Standard Deviation 163.06	-18.3 dyn*sec/cm^5 Standard Deviation 135.28

SECONDARY outcome

Timeframe: From enrollment/baseline to Week 12 in the DB treatment period

Population: Full Analysis Set(FAS): All randomized participants who received at least one dose of study drug in DB treatment, have baseline value for PVR, evaluated As per assigned treatment. Here, 'N'(number of participants analyzed included population included participants with available baseline data.

SVO2 help assess tissue oxygen delivery. It describes the percentage of oxygen bound to hemoglobin in the blood which returns to the heart. This reflects the amount of residual oxygen in the blood after oxygen extraction by the tissues throughout the body.

Outcome measures

Measure	Macitentan 10 mg n=41 Participants Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.	Placebo n=41 Participants Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period.
Change From Baseline to Week 12 in Mixed Venous Oxygen Saturation (SVO2) SVO2 at baseline	69.2 percent of oxygen bound to hemoglobin Standard Deviation 9.87	69.9 percent of oxygen bound to hemoglobin Standard Deviation 5.34
Change From Baseline to Week 12 in Mixed Venous Oxygen Saturation (SVO2) SVO2 at Week 12	70.3 percent of oxygen bound to hemoglobin Standard Deviation 7.07	70.7 percent of oxygen bound to hemoglobin Standard Deviation 8.58
Change From Baseline to Week 12 in Mixed Venous Oxygen Saturation (SVO2) Change in SVO2 from baseline to Week 12	1.1 percent of oxygen bound to hemoglobin Standard Deviation 6.70	0.8 percent of oxygen bound to hemoglobin Standard Deviation 7.81

Adverse Events

Double-Blind (DB) Period: Macitentan 10 mg

Serious events: 9 serious events

Other events: 34 other events

Deaths: 0 deaths

DB Period: Placebo

Serious events: 6 serious events

Other events: 32 other events

Deaths: 0 deaths

Open-Label (OL) Period: Macitentan 10 mg

Serious events: 18 serious events

Other events: 62 other events

Deaths: 4 deaths

OL Extension Period: Macitentan 10 mg

Serious events: 11 serious events

Other events: 30 other events

Deaths: 2 deaths

Serious adverse events

Measure	Double-Blind (DB) Period: Macitentan 10 mg n=43 participants at risk Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks during DB treatment period.	DB Period: Placebo n=42 participants at risk Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks during DB treatment period.	Open-Label (OL) Period: Macitentan 10 mg n=80 participants at risk Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. Participants who completed DB treatment period continued to receive macitentan 10 mg for 12 weeks (up to Week 24) in OL treatment period.	OL Extension Period: Macitentan 10 mg n=33 participants at risk Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. Participants who completed DB treatment period continued to receive macitentan 10 mg for 12 weeks (up to Week 24) in OL treatment period . Participants (who were randomized at French sites) who completed the core phase of the study as scheduled and opted to continue receiving OL study treatment continued to receive macitentan 10 mg in OLE period.
Blood and lymphatic system disorders Anaemia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.5% 2/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Iron Deficiency Anaemia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Cardiac disorders Atrial Fibrillation	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Cardiac disorders Left Ventricular Failure	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Cardiac disorders Right Ventricular Failure	4.7% 2/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.5% 2/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	6.1% 2/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Ear and labyrinth disorders Tinnitus	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal Pain	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Ascites	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Duodenal Vascular Ectasia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Gastrointestinal Angiodysplasia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Ileus	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Intestinal Obstruction	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Melaena	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.5% 2/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Portal Hypertensive Gastropathy	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Death	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Localised Oedema	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Oedema Peripheral	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Hepatobiliary disorders Hepatic Failure	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Immune system disorders Hypersensitivity	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Bronchitis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Escherichia Pyelonephritis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Gastroenteritis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Lung Infection	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Pneumonia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Staphylococcal Infection	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Urosepsis	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Fall	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Humerus Fracture	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Subdural Haematoma	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Liver Function Test Increased	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Troponin I Increased	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Diabetes Mellitus	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Fluid Overload	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Intervertebral Disc Protrusion	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Osteitis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular Carcinoma	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	4.8% 2/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Ascites	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal Adenocarcinoma	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Testis Cancer	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Haemorrhagic Stroke	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Hepatic Encephalopathy	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.5% 2/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	6.1% 2/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Presyncope	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Syncope	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Renal and urinary disorders Acute Kidney Injury	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Renal and urinary disorders Chronic Kidney Disease	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Reproductive system and breast disorders Priapism	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Acute Pulmonary Oedema	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Alveolitis	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Asthma	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Haemoptysis	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary Arterial Hypertension	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary Toxicity	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Localised Infection	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Vascular Procedure Complication	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Surgical and medical procedures Aneurysm Repair	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.

Other adverse events

Measure	Double-Blind (DB) Period: Macitentan 10 mg n=43 participants at risk Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks during DB treatment period.	DB Period: Placebo n=42 participants at risk Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks during DB treatment period.	Open-Label (OL) Period: Macitentan 10 mg n=80 participants at risk Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. Participants who completed DB treatment period continued to receive macitentan 10 mg for 12 weeks (up to Week 24) in OL treatment period.	OL Extension Period: Macitentan 10 mg n=33 participants at risk Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. Participants who completed DB treatment period continued to receive macitentan 10 mg for 12 weeks (up to Week 24) in OL treatment period . Participants (who were randomized at French sites) who completed the core phase of the study as scheduled and opted to continue receiving OL study treatment continued to receive macitentan 10 mg in OLE period.
Blood and lymphatic system disorders Anaemia	4.7% 2/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	11.2% 9/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	15.2% 5/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Increased Tendency to Bruise	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Iron Deficiency Anaemia	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Leukopenia	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Neutropenia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Cardiac disorders Arrhythmia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Cardiac disorders Atrial Fibrillation	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Cardiac disorders Bradycardia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Cardiac disorders Cyanosis	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Cardiac disorders Palpitations	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	6.1% 2/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Cardiac disorders Pericarditis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Cardiac disorders Right Ventricular Failure	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Cardiac disorders Tachycardia	4.7% 2/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Ear and labyrinth disorders Ear Pain	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Ear and labyrinth disorders Tinnitus	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Ear and labyrinth disorders Vertigo	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Eye disorders Cataract	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Eye disorders Conjunctival Hyperaemia	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Eye disorders Diabetic Retinopathy	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Eye disorders Diplopia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Eye disorders Dry Eye	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.5% 2/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Eye disorders Eye Irritation	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Eye disorders Eye Oedema	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Eye disorders Eye Pruritus	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Eye disorders Eye Swelling	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Eye disorders Meibomian Gland Dysfunction	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Eye disorders Vision Blurred	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal Pain	4.7% 2/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal Pain Upper	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Anal Polyp	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Ascites	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.5% 2/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Constipation	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Diarrhoea	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	9.5% 4/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Dry Mouth	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	4.8% 2/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Duodenal Polyp	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Gastritis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Gastritis Erosive	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Gastrooesophageal Reflux Disease	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Gingival Bleeding	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Nausea	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	4.8% 2/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.8% 3/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Pancreatic Cyst	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Portal Hypertensive Gastropathy	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Rectal Haemorrhage	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Varices Oesophageal	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Vomiting	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.5% 2/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Asthenia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	5.0% 4/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	9.1% 3/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Chest Pain	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Face Oedema	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Fatigue	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.5% 2/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Generalised Oedema	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Influenza Like Illness	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.8% 3/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	6.1% 2/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Localised Oedema	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Malaise	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Non-Cardiac Chest Pain	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Oedema Peripheral	23.3% 10/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	11.9% 5/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	16.2% 13/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	15.2% 5/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Pain	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Peripheral Swelling	4.7% 2/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Swelling	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
General disorders Temperature Intolerance	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Hepatobiliary disorders Biliary Colic	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Hepatobiliary disorders Cholelithiasis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Hepatobiliary disorders Hepatic Mass	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Hepatobiliary disorders Jaundice	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Hepatobiliary disorders Portal Vein Thrombosis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Bacterial Infection	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Bronchitis	9.3% 4/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.8% 3/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	39.4% 13/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Candida Infection	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Conjunctivitis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Fungal Infection	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Furuncle	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Gastroenteritis	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Gastrointestinal Infection	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Herpes Virus Infection	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Herpes Zoster	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Influenza	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Laryngitis	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Lower Respiratory Tract Infection	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Nasopharyngitis	4.7% 2/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	4.8% 2/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.8% 3/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	6.1% 2/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Periodontitis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Rhinitis	4.7% 2/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	5.0% 4/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	21.2% 7/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Sinusitis	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	6.1% 2/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Sinusitis Fungal	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Tonsillitis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Tooth Abscess	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Urinary Tract Infection	4.7% 2/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Anaemia Postoperative	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Contusion	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Eye Contusion	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Fall	4.7% 2/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Foot Fracture	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	4.8% 2/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Head Injury	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Limb Injury	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Tooth Fracture	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Ammonia Increased	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Aspartate Aminotransferase Increased	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Blood Bilirubin Increased	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Blood Creatinine Increased	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Blood Glucose Increased	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Blood Potassium Decreased	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Blood Potassium Increased	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Blood Sodium Decreased	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Blood Uric Acid Increased	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Blood Urine Present	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Brain Natriuretic Peptide Increased	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Coronavirus Test Positive	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Haematocrit Decreased	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Haemoglobin Decreased	7.0% 3/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.8% 3/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Intestinal Transit Time Decreased	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Liver Function Test Abnormal	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Oxygen Saturation Decreased	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Platelet Count Decreased	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Total Bile Acids Increased	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Urine Output Decreased	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Decreased Appetite	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Fluid Retention	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Folate Deficiency	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Gout	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypokalaemia	4.7% 2/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	14.3% 6/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.5% 2/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	6.1% 2/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypomagnesaemia	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Iron Deficiency	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Magnesium Deficiency	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Vitamin D Deficiency	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.5% 2/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Back Pain	4.7% 2/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	6.1% 2/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Bone Pain	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Dupuytren's Contracture	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Joint Swelling	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Muscle Spasms	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	11.9% 5/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.8% 3/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.5% 2/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal Stiffness	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Myalgia	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Neck Pain	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.5% 2/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Pain in Extremity	4.7% 2/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	7.1% 3/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	7.5% 6/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Pain in Jaw	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Sebaceous Adenoma	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Balance Disorder	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Dizziness	4.7% 2/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	4.8% 2/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	6.2% 5/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Headache	16.3% 7/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	16.7% 7/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	12.5% 10/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Hepatic Encephalopathy	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Hypoaesthesia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Intracranial Aneurysm	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Lethargy	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Neuralgia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Presyncope	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Restless Legs Syndrome	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Sciatica	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Syncope	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Nervous system disorders Tremor	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Psychiatric disorders Alcohol Abuse	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Psychiatric disorders Depression	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Psychiatric disorders Insomnia	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	15.2% 5/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Renal and urinary disorders Acute Kidney Injury	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Renal and urinary disorders Oliguria	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Renal and urinary disorders Renal Failure	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Reproductive system and breast disorders Breast Mass	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Reproductive system and breast disorders Uterine Haemorrhage	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Bendopnoea	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	7.1% 3/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dry Throat	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	4.8% 2/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.8% 3/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	9.1% 3/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea Exertional	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.8% 3/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.5% 2/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	6.1% 2/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Nasal Dryness	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Nasal Obstruction	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	9.1% 3/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Portopulmonary Hypertension	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary Arterial Hypertension	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Sinus Congestion	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Sleep Apnoea Syndrome	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Sneezing	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Blister	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Dermal Cyst	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Hyperkeratosis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.8% 3/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Rash	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.5% 2/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Umbilical Haemorrhage	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	1.2% 1/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Vitiligo	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Social circumstances Alcohol Use	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Surgical and medical procedures Inguinal Hernia Repair	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Surgical and medical procedures Oesophageal Variceal Ligation	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Vascular disorders Flushing	2.3% 1/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Vascular disorders Haematoma	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Vascular disorders Hypotension	4.7% 2/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.8% 3/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Vascular disorders Peripheral Venous Disease	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	3.0% 1/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Eye disorders Conjunctival Haemorrhage	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Eye disorders Lacrimation Decreased	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal Discomfort	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal Distension	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Glossodynia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Groin Abscess	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Onychomycosis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Infections and infestations Pharyngitis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Joint Dislocation	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Procedural Pain	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Intestinal Transit Time Abnormal	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Venous Pressure Jugular Increased	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Investigations Weight Increased	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Psychiatric disorders Sleep Disorder	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Renal and urinary disorders Chromaturia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Reproductive system and breast disorders Gynaecomastia	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Throat Irritation	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Surgical and medical procedures Injection	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Surgical and medical procedures Skin Neoplasm Excision	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.
Vascular disorders Orthostatic Hypotension	0.00% 0/43 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	2.4% 1/42 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/80 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.	0.00% 0/33 • Up to 3.4 years The Safety Set (SS) included all participants who received at least one dose of study treatment.

Additional Information

Clinical Trial Disclosure Desk

Actelion Pharmaceuticals Ltd.

Phone: +41 61 565 6565

Email: clinical-trials-disclosure@its.jnj.com

Results disclosure agreements

• Principal investigator is a sponsor employee Any study-related publication written independently by investigators must be submitted to Actelion for review at least 30 days prior to submission for publication or presentation. Upon review, Actelion may provide comments, and may also request alterations and/or deletions for the sole purpose of protecting its confidential information and/or patent rights.
• Publication restrictions are in place

Restriction type: OTHER