Trial Outcomes & Findings for Pacritinib Versus Best Available Therapy to Treat Patients With Myelofibrosis and Thrombocytopenia (NCT NCT02055781)

NCT ID: NCT02055781

Last Updated: 2021-11-18

Results Overview

Proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to week 24 as measured by magnetic resonance imaging (MRI) or computed tomography (CT).

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

311 participants

Primary outcome timeframe

Baseline to Week 24

Results posted on

2021-11-18

Participant Flow

Participant milestones

Participant milestones
Measure	Pacritinib, QD Pacritinib 400 mg QD	Pacritinib, BID Pacritinib 200 mg BID	Best Available Therapy BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry
Overall Study STARTED	104	107	100
Overall Study COMPLETED	62	79	63
Overall Study NOT COMPLETED	42	28	37

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pacritinib Versus Best Available Therapy to Treat Patients With Myelofibrosis and Thrombocytopenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pacritinib, Once Daily n=104 Participants Pacritinib 400 mg, once daily	Pacritinib, Twice Daily n=107 Participants Pacritinib 200 mg, twice daily	Best Available Therapy n=100 Participants BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry.	Total n=311 Participants Total of all reporting groups
Age, Categorical <=18 years	32 Participants n=5 Participants	41 Participants n=7 Participants	32 Participants n=5 Participants	105 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	70 Participants n=5 Participants	65 Participants n=7 Participants	68 Participants n=5 Participants	203 Participants n=4 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Age, Continuous	69 years STANDARD_DEVIATION 8.55 • n=5 Participants	65.9 years STANDARD_DEVIATION 8.75 • n=7 Participants	66.9 years STANDARD_DEVIATION 9.75 • n=5 Participants	67.2 years STANDARD_DEVIATION 9.01 • n=4 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	44 Participants n=7 Participants	45 Participants n=5 Participants	140 Participants n=4 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	63 Participants n=7 Participants	55 Participants n=5 Participants	171 Participants n=4 Participants
Region of Enrollment New Zealand	4 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	13 Participants n=4 Participants
Region of Enrollment Canada	5 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants
Region of Enrollment Netherlands	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment Belgium	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Region of Enrollment Hungary	9 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	24 Participants n=4 Participants
Region of Enrollment United States	44 Participants n=5 Participants	44 Participants n=7 Participants	43 Participants n=5 Participants	131 Participants n=4 Participants
Region of Enrollment Czechia	2 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants
Region of Enrollment United Kingdom	5 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	27 Participants n=4 Participants
Region of Enrollment Australia	4 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Region of Enrollment France	8 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	27 Participants n=4 Participants
Region of Enrollment Germany	10 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	17 Participants n=4 Participants
Region of Enrollment Russia	11 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	30 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24

Proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to week 24 as measured by magnetic resonance imaging (MRI) or computed tomography (CT).

Outcome measures

Outcome measures
Measure	Pacritinib, Once Daily n=75 Participants Pacritinib 400 mg, once daily	Pacritinib, Twice Daily n=74 Participants Pacritinib 200 mg, twice daily	Best Available Therapy n=72 Participants BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry
Spleen Volume Reduction	11 Participants	16 Participants	2 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24

Proportion of patients achieving a ≥ 50% reduction in the total symptom score from baseline to Week 24 on the Myeloproliferative Neoplasm Symptom Assessment Form 2.0 (MPN-SAF TSS 2.0). Responses (on a scale from 0 \[absent\] to 10 \[worst imaginable\]) to questions about symptoms (tiredness, early satiety, abdominal discomfort, night sweats, pruritus, bone pain, and pain under the ribs on the left side) were used to calculate the TSS.

Outcome measures

Outcome measures
Measure	Pacritinib, Once Daily n=75 Participants Pacritinib 400 mg, once daily	Pacritinib, Twice Daily n=74 Participants Pacritinib 200 mg, twice daily	Best Available Therapy n=72 Participants BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry
Total Symptom Score (TSS) Reduction	13 Participants	24 Participants	10 Participants

Adverse Events

Pacritinib, Once Daily

Serious events: 48 serious events

Other events: 104 other events

Deaths: 22 deaths

Pacritinib, Twice Daily

Serious events: 50 serious events

Other events: 100 other events

Deaths: 20 deaths

Best Available Therapy

Serious events: 30 serious events

Other events: 87 other events

Deaths: 20 deaths

Serious adverse events

Other adverse events

Additional Information

Beth Ziemba

CTI BioPharma Corp.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Pacritinib, Once Daily n=104 participants at risk Pacritinib 400 mg, once daily	Pacritinib, Twice Daily n=106 participants at risk Pacritinib 200 mg, twice daily	Best Available Therapy n=98 participants at risk BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry
Nervous system disorders Transient ischaemic attack	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Gastrointestinal disorders Oesophageal varices haemorrhage	0.96% 1/104 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.94% 1/106 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Vascular disorders Deep vein Thrombosis	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.94% 1/106 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.0% 2/98 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.8% 3/106 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/98 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.94% 1/106 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelofibrosis	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
General disorders Disease progression	3.8% 4/104 • Number of events 4 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.8% 3/106 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	3.1% 3/98 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
General disorders Pyrexia	1.9% 2/104 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.8% 3/106 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.0% 2/98 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
General disorders Oedema peripheral	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Psychiatric disorders confusional state	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Psychiatric disorders Mental status changes	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Injury, poisoning and procedural complications Splenic rupture	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Cardiac disorders Cardiac failure	0.96% 1/104 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	3.8% 4/106 • Number of events 4 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.0% 2/98 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Cardiac disorders Atrial fibrillation	2.9% 3/104 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	3.1% 3/98 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Cardiac disorders Atrial flutter	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Cardiac disorders Supraventricular tachycardia	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Blood and lymphatic system disorders Anaemia	4.8% 5/104 • Number of events 5 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	7.5% 8/106 • Number of events 8 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	3.1% 3/98 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Blood and lymphatic system disorders Thrombocytopenia	1.9% 2/104 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	5.7% 6/106 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.0% 2/98 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Blood and lymphatic system disorders Febrile neutropenia	0.96% 1/104 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.94% 1/106 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.0% 2/98 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Blood and lymphatic system disorders Neutropenia	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.94% 1/106 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Respiratory, thoracic and mediastinal disorders Epistaxis	1.9% 2/104 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.9% 2/106 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.96% 1/104 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.94% 1/106 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.96% 1/104 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.96% 1/104 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Gastrointestinal disorders Abdominal pain	1.9% 2/104 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/98 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Gastrointestinal disorders Haemorrholdal haemorrhage	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Gastrointestinal disorders Melaena	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Renal and urinary disorders Renal failure acute	4.8% 5/104 • Number of events 5 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.9% 2/106 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.0% 2/98 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Hepatobiliary disorders Cholecystitis	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Hepatobiliary disorders Jaundice	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Skin and subcutaneous tissue disorders Rash	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Musculoskeletal and connective tissue disorders Periarthrtis	0.00% 0/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Metabolism and nutrition disorders Decreased appetite	0.96% 1/104 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Metabolism and nutrition disorders Failure to thrive	1.9% 2/104 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).

Other adverse events
Measure	Pacritinib, Once Daily n=104 participants at risk Pacritinib 400 mg, once daily	Pacritinib, Twice Daily n=106 participants at risk Pacritinib 200 mg, twice daily	Best Available Therapy n=98 participants at risk BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry
Injury, poisoning and procedural complications Contusion	6.7% 7/104 • Number of events 7 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	9.4% 10/106 • Number of events 10 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	8.2% 8/98 • Number of events 8 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Injury, poisoning and procedural complications Fall	6.7% 7/104 • Number of events 7 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	4.7% 5/106 • Number of events 5 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	3.1% 3/98 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Investigations Weight decreased	3.8% 4/104 • Number of events 4 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	6.6% 7/106 • Number of events 7 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	3.1% 3/98 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Respiratory, thoracic and mediastinal disorders Epistaxis	10.6% 11/104 • Number of events 11 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	12.3% 13/106 • Number of events 13 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	13.3% 13/98 • Number of events 13 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Respiratory, thoracic and mediastinal disorders Cough	10.6% 11/104 • Number of events 11 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	8.5% 9/106 • Number of events 9 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	10.2% 10/98 • Number of events 10 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.7% 9/104 • Number of events 9 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	10.4% 11/106 • Number of events 11 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	9.2% 9/98 • Number of events 9 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Blood and lymphatic system disorders Thrombocytopenia	32.7% 34/104 • Number of events 34 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	34.0% 36/106 • Number of events 36 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	23.5% 23/98 • Number of events 23 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Blood and lymphatic system disorders Anaemia	27.9% 29/104 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	23.6% 25/106 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	15.3% 15/98 • Number of events 15 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Blood and lymphatic system disorders Neutropenia	8.7% 9/104 • Number of events 9 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	8.5% 9/106 • Number of events 9 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	6.1% 6/98 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Nervous system disorders Dizziness	14.4% 15/104 • Number of events 15 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	15.1% 16/106 • Number of events 16 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	5.1% 5/98 • Number of events 5 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Nervous system disorders Dysgeusia	7.7% 8/104 • Number of events 8 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	7.5% 8/106 • Number of events 8 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.00% 0/98 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Nervous system disorders Headache	5.8% 6/104 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	8.5% 9/106 • Number of events 9 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	5.1% 5/98 • Number of events 5 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
General disorders Fatigue	17.3% 18/104 • Number of events 18 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	17.0% 18/106 • Number of events 18 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	16.3% 16/98 • Number of events 16 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
General disorders Oedema peripheral	13.5% 14/104 • Number of events 14 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	19.8% 21/106 • Number of events 21 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	15.3% 15/98 • Number of events 15 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
General disorders Asthenia	4.8% 5/104 • Number of events 5 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.8% 3/106 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	6.1% 6/98 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
General disorders Early satiety	0.96% 1/104 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.8% 3/106 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	5.1% 5/98 • Number of events 5 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
General disorders Pyrexia	10.6% 11/104 • Number of events 11 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	15.1% 16/106 • Number of events 16 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	3.1% 3/98 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Psychiatric disorders Insomnia	11.5% 12/104 • Number of events 12 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	9.4% 10/106 • Number of events 10 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	4.1% 4/98 • Number of events 4 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Gastrointestinal disorders Diarrhoea	67.3% 70/104 • Number of events 70 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	48.1% 51/106 • Number of events 51 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	15.3% 15/98 • Number of events 15 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Gastrointestinal disorders Nausea	37.5% 39/104 • Number of events 39 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	32.1% 34/106 • Number of events 34 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	11.2% 11/98 • Number of events 11 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Gastrointestinal disorders Vomiting	21.2% 22/104 • Number of events 22 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	18.9% 20/106 • Number of events 20 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	5.1% 5/98 • Number of events 5 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Gastrointestinal disorders Abdominal pain	19.2% 20/104 • Number of events 20 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	9.4% 10/106 • Number of events 10 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	19.4% 19/98 • Number of events 19 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Gastrointestinal disorders Abdmonial distension	2.9% 3/104 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	5.7% 6/106 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	6.1% 6/98 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Gastrointestinal disorders Abdominal pain upper	5.8% 6/104 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	5.7% 6/106 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	6.1% 6/98 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Gastrointestinal disorders Constipation	14.4% 15/104 • Number of events 15 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	7.5% 8/106 • Number of events 8 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	6.1% 6/98 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Skin and subcutaneous tissue disorders Pruritus	9.6% 10/104 • Number of events 10 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	10.4% 11/106 • Number of events 11 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	6.1% 6/98 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Skin and subcutaneous tissue disorders Rash	5.8% 6/104 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	7.5% 8/106 • Number of events 8 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	5.1% 5/98 • Number of events 5 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Skin and subcutaneous tissue disorders Night sweats	7.7% 8/104 • Number of events 8 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	7.5% 8/106 • Number of events 8 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	6.1% 6/98 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Musculoskeletal and connective tissue disorders Arthralgia	7.7% 8/104 • Number of events 8 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	8.5% 9/106 • Number of events 9 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	3.1% 3/98 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Musculoskeletal and connective tissue disorders Bone pain	4.8% 5/104 • Number of events 5 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	6.6% 7/106 • Number of events 7 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	7.1% 7/98 • Number of events 7 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Musculoskeletal and connective tissue disorders Pain in extremity	6.7% 7/104 • Number of events 7 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	9.4% 10/106 • Number of events 10 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	6.1% 6/98 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Metabolism and nutrition disorders Decreased appetite	12.5% 13/104 • Number of events 13 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	12.3% 13/106 • Number of events 13 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	11.2% 11/98 • Number of events 11 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Infections and infestations Upper respiratory tract infection	7.7% 8/104 • Number of events 8 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	10.4% 11/106 • Number of events 11 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	6.1% 6/98 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Eye disorders Conjunctival haemorrhage	2.9% 3/104 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	5.7% 6/106 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	4.1% 4/98 • Number of events 4 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Gastrointestinal disorders Gastrooesophageal reflux disease	5.8% 6/104 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	0.94% 1/106 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.0% 2/98 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Infections and infestations Pneumonia	7.7% 8/104 • Number of events 8 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	8.5% 9/106 • Number of events 9 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	4.1% 4/98 • Number of events 4 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Infections and infestations Urinary tract infection	7.7% 8/104 • Number of events 8 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	3.8% 4/106 • Number of events 4 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.0% 2/98 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Infections and infestations Bronchitis	2.9% 3/104 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	5.7% 6/106 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	3.1% 3/98 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Investigations Electrocardiogram QT prolonged	5.8% 6/104 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.9% 2/106 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.0% 2/98 • Number of events 2 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).
Metabolism and nutrition disorders Hyperuricaemia	5.8% 6/104 • Number of events 6 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	2.8% 3/106 • Number of events 3 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).	1.0% 1/98 • Number of events 1 • From the time of signing informed consent through 30 days after the last study treatment. All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).