Trial Outcomes & Findings for Study of the Safety and Pharmacokinetics of BGB-3111 in Subjects With B-Cell Lymphoid Malignancies (NCT NCT02343120)

Last Updated: 2022-04-28

Results Overview

Number of participants with adverse events and serious adverse events, including clinically relevant physical examinations and laboratory measurements

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

385 participants

Primary outcome timeframe

Up to approximately 6 years and 7 months

Results posted on

2022-04-28

Participant Flow

The study was conducted in 2 parts. The dose escalation part (Part 1) determined the recommended phase 2 dose (RP2D) and regimen and the dose expansion part (Part 2) further characterized the safety and efficacy at the RP2D.

Participant milestones

Participant milestones
Measure	Part 1: 40 mg QD Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1 and Part 2: 160 mg BID Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up were evaluated. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Part 1 and Part 2: 320 mg QD Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up were evaluated. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1: Dose Escalation STARTED	3	4	5	4	1
Part 1: Dose Escalation COMPLETED	0	0	0	0	0
Part 1: Dose Escalation NOT COMPLETED	3	4	5	4	1
Part 2: Expansion STARTED	0	0	0	274	94
Part 2: Expansion COMPLETED	0	0	0	0	0
Part 2: Expansion NOT COMPLETED	0	0	0	274	94

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: 40 mg QD Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1 and Part 2: 160 mg BID Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up were evaluated. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Part 1 and Part 2: 320 mg QD Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up were evaluated. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1: Dose Escalation Sponsor decision	1	2	3	2	0
Part 1: Dose Escalation Death	1	2	2	2	1
Part 1: Dose Escalation Lost to Follow-up	1	0	0	0	0
Part 2: Expansion Sponsor decision	0	0	0	165	67
Part 2: Expansion Death	0	0	0	74	17
Part 2: Expansion Withdrawal by Subject	0	0	0	28	2
Part 2: Expansion Lost to Follow-up	0	0	0	5	2
Part 2: Expansion Other	0	0	0	1	5
Part 2: Expansion Adverse Event	0	0	0	1	1

Baseline Characteristics

Study of the Safety and Pharmacokinetics of BGB-3111 in Subjects With B-Cell Lymphoid Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: 40 mg QD n=3 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD n=4 Participants Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD n=5 Participants Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1 and Part 2: 160 mg BID n=278 Participants Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up were evaluated. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Part 1 and Part 2: 320 mg QD n=95 Participants Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up were evaluated. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Total n=385 Participants Total of all reporting groups
Age, Continuous	62.7 Years STANDARD_DEVIATION 9.45 • n=5 Participants	62.3 Years STANDARD_DEVIATION 14.38 • n=7 Participants	72.6 Years STANDARD_DEVIATION 8.88 • n=5 Participants	66.4 Years STANDARD_DEVIATION 11.21 • n=4 Participants	65.8 Years STANDARD_DEVIATION 11.24 • n=21 Participants	66.3 Years STANDARD_DEVIATION 11.19 • n=10 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	86 Participants n=4 Participants	20 Participants n=21 Participants	109 Participants n=10 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	192 Participants n=4 Participants	75 Participants n=21 Participants	276 Participants n=10 Participants
Race/Ethnicity, Customized White	2 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	205 Participants n=4 Participants	87 Participants n=21 Participants	303 Participants n=10 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	47 Participants n=4 Participants	5 Participants n=21 Participants	53 Participants n=10 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	1 Participants n=21 Participants	5 Participants n=10 Participants
Race/Ethnicity, Customized Native Hawaiians or other Pacific Islanders	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	18 Participants n=4 Participants	2 Participants n=21 Participants	20 Participants n=10 Participants

PRIMARY outcome

Timeframe: Up to approximately 6 years and 7 months

Population: The Safety Analysis Set included all participants who received ≥ 1 dose of study drug

Number of participants with adverse events and serious adverse events, including clinically relevant physical examinations and laboratory measurements

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=3 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD n=4 Participants Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD n=5 Participants Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID n=278 Participants Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD n=95 Participants Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Number of Participants With Adverse Events At least one treatment-emergent adverse event	3 Participants	4 Participants	5 Participants	274 Participants	94 Participants
Part 1 and Part 2: Number of Participants With Adverse Events Serious adverse events	1 Participants	2 Participants	3 Participants	157 Participants	45 Participants

PRIMARY outcome

Timeframe: Month 9

Population: The Safety Analysis Set included all participants who received ≥ 1 dose of study drug

RP2D for zanubrutinib was the maximum tolerated dose (MTD) or less, which was determined by testing increasing doses up to 320 mg QD

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=17 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1: Recommended Phase 2 Dose (RP2D) for Zanubrutinib	320 milligrams	—	—	—	—

SECONDARY outcome

Timeframe: Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours

Population: The pharmacokinetic (PK) analysis set included all participants for whom valid zanubrutinib PK parameters could be estimated, shown as overall number analyzed. Only participants with available data per dose were included in the analysis.

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=3 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD n=4 Participants Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD n=5 Participants Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID n=76 Participants Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD n=19 Participants Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Area Under the Curve From Time 0 to the Last Sampling Time Point Within the Dose Interval (AUClast) of Zanubrutinib	274.7 nanograms/milliliters*hour Geometric Coefficient of Variation 47.8	436.8 nanograms/milliliters*hour Geometric Coefficient of Variation 103.5	1480 nanograms/milliliters*hour Geometric Coefficient of Variation 53.0	1132 nanograms/milliliters*hour Geometric Coefficient of Variation 61.1	2281 nanograms/milliliters*hour Geometric Coefficient of Variation 60.5

SECONDARY outcome

Timeframe: Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours

Population: The PK analysis set included all participants for whom valid zanubrutinib PK parameters could be estimated, shown as overall number analyzed. Only participants with available data per dose were included in the analysis.

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=3 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD n=4 Participants Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD n=5 Participants Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID n=59 Participants Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD n=18 Participants Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Area Under the Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Zanubrutinib	301.1 nanograms/milliliters*hour Geometric Coefficient of Variation 51.5	460.0 nanograms/milliliters*hour Geometric Coefficient of Variation 100.6	1505 nanograms/milliliters*hour Geometric Coefficient of Variation 52.7	1253 nanograms/milliliters*hour Geometric Coefficient of Variation 59.0	2538 nanograms/milliliters*hour Geometric Coefficient of Variation 47.8

SECONDARY outcome

Timeframe: Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=3 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD n=4 Participants Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD n=5 Participants Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID n=76 Participants Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD n=19 Participants Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) After Administration of Zanubrutinib	86.0 nanograms/milliliter Geometric Coefficient of Variation 46.6	125 nanograms/milliliter Geometric Coefficient of Variation 77.6	397 nanograms/milliliter Geometric Coefficient of Variation 76.1	304 nanograms/milliliter Geometric Coefficient of Variation 63.8	566 nanograms/milliliter Geometric Coefficient of Variation 65.6

SECONDARY outcome

Timeframe: Week 2 Day 1 pre-dose and 24 hours

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=3 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD n=4 Participants Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD n=5 Participants Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID n=77 Participants Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD n=72 Participants Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) After Administration of Zanubrutinib	75.7 nanograms/milliliter Geometric Coefficient of Variation 36.2	169 nanograms/milliliter Geometric Coefficient of Variation 50.0	387 nanograms/milliliter Geometric Coefficient of Variation 60.7	299 nanograms/milliliter Geometric Coefficient of Variation 56.1	533 nanograms/milliliter Geometric Coefficient of Variation 55.0

SECONDARY outcome

Timeframe: Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=3 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD n=4 Participants Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD n=5 Participants Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID n=76 Participants Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD n=19 Participants Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib	1.00 Hours Interval 0.5 to 1.98	2.00 Hours Interval 1.17 to 2.0	1.92 Hours Interval 0.93 to 2.08	2.00 Hours Interval 0.83 to 8.0	2.00 Hours Interval 0.72 to 3.08

SECONDARY outcome

Timeframe: Week 2 Day 1 pre-dose and 24 hours

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=3 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD n=4 Participants Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD n=5 Participants Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID n=77 Participants Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD n=72 Participants Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib	2.00 Hours Interval 2.0 to 2.0	2.50 Hours Interval 1.08 to 3.0	2.00 Hours Interval 1.0 to 3.17	2.00 Hours Interval 0.53 to 6.0	2.00 Hours Interval 0.33 to 6.0

SECONDARY outcome

Timeframe: Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=3 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD n=4 Participants Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD n=5 Participants Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID n=59 Participants Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD n=18 Participants Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Zanubrutinib	1.94 Hours Geometric Coefficient of Variation 28.5	1.97 Hours Geometric Coefficient of Variation 29.8	3.87 Hours Geometric Coefficient of Variation 24.9	2.73 Hours Geometric Coefficient of Variation 60.2	3.30 Hours Geometric Coefficient of Variation 61.2

SECONDARY outcome

Timeframe: Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=3 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD n=4 Participants Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD n=5 Participants Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID n=61 Participants Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD n=18 Participants Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Apparent Clearance (CL/F) of Zanubrutinib	133 Liters/hour Geometric Coefficient of Variation 51.5	174 Liters/hour Geometric Coefficient of Variation 100.6	106 Liters/hour Geometric Coefficient of Variation 52.7	128 Liters/hour Geometric Coefficient of Variation 59.4	126 Liters/hour Geometric Coefficient of Variation 47.8

SECONDARY outcome

Timeframe: Week 1 Day 1 pre-dose, 0.5, 1, 2, 3, 4, and 8 hours

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=3 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD n=4 Participants Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD n=5 Participants Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID n=61 Participants Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD n=18 Participants Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Apparent Volume of Distribution of Zanubrutinib During the Terminal Phase (Vz/F)	371 Liters Geometric Coefficient of Variation 47.5	494 Liters Geometric Coefficient of Variation 78.9	593 Liters Geometric Coefficient of Variation 61.6	530 Liters Geometric Coefficient of Variation 70.0	600 Liters Geometric Coefficient of Variation 97.6

SECONDARY outcome

Timeframe: Up to 6 years and 7 months

Population: Efficacy Evaluable Set consists of all participants who received at least one dose of zanubrutinib; for WM, participants also must have a baseline IgM (or M-protein) ≥ 5 g/L and no prior exposure to a BTK inhibitor.

ORR is defined as the percentage of participants with partial or complete response (CR), as assessed by the investigator. For CLL/SLL, ORR includes partial response (PR) with lymphocytosis (PR-L) or better (includes PR-L, PR, nodular PR or nPR and CR with incomplete marrow recovery or CRi) and for MW, ORR includes minor response or better. Efficacy results are reported for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=378 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Overall Response Rate (ORR) CLL/SLL	95.2 Percentage of participants Interval 89.8 to 98.2	—	—	—	—
Part 1 and Part 2: Overall Response Rate (ORR) WM	95.9 Percentage of participants Interval 88.5 to 99.1	—	—	—	—
Part 1 and Part 2: Overall Response Rate (ORR) MCL	82.5 Percentage of participants Interval 70.1 to 91.3	—	—	—	—
Part 1 and Part 2: Overall Response Rate (ORR) MZL	85.0 Percentage of participants Interval 62.1 to 96.8	—	—	—	—
Part 1 and Part 2: Overall Response Rate (ORR) FL	36.4 Percentage of participants Interval 20.4 to 54.9	—	—	—	—
Part 1 and Part 2: Overall Response Rate (ORR) DLBCL	42.2 Percentage of participants Interval 27.7 to 57.8	—	—	—	—
Part 1 and Part 2: Overall Response Rate (ORR) RT	61.5 Percentage of participants Interval 31.6 to 86.1	—	—	—	—
Part 1 and Part 2: Overall Response Rate (ORR) HCL	58.3 Percentage of participants Interval 27.7 to 84.8	—	—	—	—

SECONDARY outcome

Timeframe: Up to 6 years and 7 months

CRR is defined as the percentage of participants who achieve a complete response, as assessed by the investigator. For CLL/SLL, CRR includes CRi or better. For WM, CRR includes very good partial response (VGPR) or better. Efficacy results are reported for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=378 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Complete Response Rate (CRR) CLL/SLL	16.8 Percentage of participants Interval 10.7 to 24.5	—	—	—	—
Part 1 and Part 2: Complete Response Rate (CRR) WM	46.6 Percentage of participants Interval 34.8 to 58.6	—	—	—	—
Part 1 and Part 2: Complete Response Rate (CRR) MCL	28.1 Percentage of participants Interval 17.0 to 41.5	—	—	—	—
Part 1 and Part 2: Complete Response Rate (CRR) MZL	20.0 Percentage of participants Interval 5.7 to 43.7	—	—	—	—
Part 1 and Part 2: Complete Response Rate (CRR) FL	18.2 Percentage of participants Interval 7.0 to 35.5	—	—	—	—
Part 1 and Part 2: Complete Response Rate (CRR) DLBCL	24.4 Percentage of participants Interval 12.9 to 39.5	—	—	—	—
Part 1 and Part 2: Complete Response Rate (CRR) RT	15.4 Percentage of participants Interval 1.9 to 45.4	—	—	—	—
Part 1 and Part 2: Complete Response Rate (CRR) HCL	16.7 Percentage of participants Interval 2.1 to 48.4	—	—	—	—

SECONDARY outcome

Timeframe: Up to 6 years and 7 months

PR or better is defined as the percentage of participants who achieve a partial response or better, as assessed by the investigator. For CLL/SLL, includes PR, nPR, CRi, CR and for WM includes PR, VGPR, and CR. Efficacy results are reported for the B-cell malignancy subtypes chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and Waldenström macroglobulinemia (WM).

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=385 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Partial Response (PR) or Better CLL/SLL	92.0 Percentage of participants Interval 85.8 to 96.1	—	—	—	—
Part 1 and Part 2: Partial Response (PR) or Better WM	82.2 Percentage of participants Interval 71.5 to 90.2	—	—	—	—

SECONDARY outcome

Timeframe: Up to 6 years and 7 months

PFS is defined as the time from the first dose date of study drug to the date of the earliest occurrence of progressive disease or death due to any cause, whichever occurs first. Efficacy results are reported for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=378 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Progression-free Survival (PFS) CLL/SLL	61.4 Months Interval 55.2 to Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Progression-free Survival (PFS) WM	NA Months Interval 48.9 to Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Progression-free Survival (PFS) MCL	27.6 Months Interval 15.4 to 45.5	—	—	—	—
Part 1 and Part 2: Progression-free Survival (PFS) MZL	NA Months Interval 17.1 to Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Progression-free Survival (PFS) FL	10.4 Months Interval 7.7 to 22.9	—	—	—	—
Part 1 and Part 2: Progression-free Survival (PFS) DLBCL	4.1 Months Interval 2.1 to 5.6	—	—	—	—
Part 1 and Part 2: Progression-free Survival (PFS) RT	17.3 Months Interval 2.8 to Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Progression-free Survival (PFS) HCL	NA Months Interval 28.7 to Data not estimable due to insufficient number of participants with events	—	—	—	—

SECONDARY outcome

Timeframe: Up to 6 years and 7 months

OS is defined as the time from the date of the first dose to death due to any cause. Efficacy results are reported for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=378 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Overall Survival (OS) CLL/SLL	NA Months Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Overall Survival (OS) WM	NA Months Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Overall Survival (OS) MCL	NA Months Interval 27.2 to Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Overall Survival (OS) MZL	NA Months Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Overall Survival (OS) FL	NA Months Interval 37.3 to Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Overall Survival (OS) DLBCL	14.7 Months Interval 5.5 to 24.8	—	—	—	—
Part 1 and Part 2: Overall Survival (OS) RT	29.3 Months Interval 4.2 to Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Overall Survival (OS) HCL	NA Months Interval 26.6 to Data not estimable due to insufficient number of participants with events	—	—	—	—

SECONDARY outcome

Timeframe: Up to 6 years and 7 months

DOR for responders is defined as time from the date of the earliest qualifying response to the date of progressive disease or death for any cause, whichever occurs earlier. Efficacy results are reported for responders (defined as PR or better, except CLL/SLL and WM) in each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; PR with lymphocytosis or better), Waldenstrom macroglobulinemia (WM; minor response or better), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=378 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Part 1 and Part 2: Duration of Response (DOR) CLL/SLL	58.6 Months Interval 52.6 to Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Duration of Response (DOR) WM	NA Months Interval 31.34 to Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Duration of Response (DOR) MCL	28.2 Months Interval 16.2 to Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Duration of Response (DOR) MZL	NA Months Interval 6.5 to Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Duration of Response (DOR) FL	NA Months Interval 8.3 to Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Duration of Response (DOR) DLBCL	14.2 Months Interval 2.8 to 26.2	—	—	—	—
Part 1 and Part 2: Duration of Response (DOR) RT	25.9 Months Interval 5.9 to Data not estimable due to insufficient number of participants with events	—	—	—	—
Part 1 and Part 2: Duration of Response (DOR) HCL	NA Months Data not estimable due to insufficient number of participants with events	—	—	—	—

SECONDARY outcome

Timeframe: Week 1 Day 1 (W1D1) predose, W1D1 4 hours, W1D2 24 hours, W1D3 predose, and W2D1 predose

Population: Pharmacodynamic analysis set consisted of participants in which PBMCs were collected and evaluable samples were obtained.

Number of participants with greater than 75% BTK occupancy of zanubrutinib in peripheral blood mononuclear cells (PBMCs)

Outcome measures

Outcome measures
Measure	Part 1: 40 mg QD n=3 Participants Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD n=4 Participants Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD n=5 Participants Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Parts 1 and 2: 160 mg BID n=21 Participants Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Parts 1 and 2: 320 mg QD n=10 Participants Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Number of Participants With Greater Than 75% Bruton's Tyrosine Kinase (BTK) Occupancy	3 Participants	4 Participants	5 Participants	20 Participants	9 Participants

Adverse Events

Part 1: 40 mg QD

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

Part 1: 80 mg QD

Serious events: 2 serious events

Other events: 4 other events

Deaths: 2 deaths

Part 1: 160 mg QD

Serious events: 3 serious events

Other events: 5 other events

Deaths: 2 deaths

Part 1 and Part 2: 160 mg BID

Serious events: 157 serious events

Other events: 273 other events

Deaths: 76 deaths

Part 1 and Part 2: 320 mg QD

Serious events: 45 serious events

Other events: 94 other events

Deaths: 19 deaths

Serious adverse events

Serious adverse events
Measure	Part 1: 40 mg QD n=3 participants at risk Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD n=4 participants at risk Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD n=5 participants at risk Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1 and Part 2: 160 mg BID n=278 participants at risk Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Part 1 and Part 2: 320 mg QD n=95 participants at risk Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Infections and infestations Infective exacerbation of bronchiectasis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Constipation	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Influenza	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.8% 5/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.5% 7/278 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Blood and lymphatic system disorders Haemolytic anaemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Blood and lymphatic system disorders Hyperviscosity syndrome	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Blood and lymphatic system disorders Lymphocytosis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Blood and lymphatic system disorders Splenomegaly	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Acute coronary syndrome	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Acute myocardial infarction	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Atrial fibrillation	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Atrial flutter	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Atrioventricular block complete	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Bradycardia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Cardiac failure	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Cardiac failure congestive	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Coronary artery stenosis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Myocardial ischaemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Palpitations	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Pericardial effusion	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Tachycardia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Ventricular extrasystoles	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Ear and labyrinth disorders Deafness	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Ear and labyrinth disorders Vertigo	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Endocrine disorders Hypercalcaemia of malignancy	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Colitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Colitis ischaemic	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.8% 5/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Dysphagia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Enteritis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Enterovesical fistula	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Gastric volvulus	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Haemorrhoids	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Hiatus hernia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Inguinal hernia strangulated	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Nausea	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Pneumatosis intestinalis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Retroperitoneal mass	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Vomiting	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Chest pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Death	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Fatigue	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Influenza like illness	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Multiple organ dysfunction syndrome	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Non-cardiac chest pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Pyrexia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 9/278 • Number of events 12 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Hepatobiliary disorders Bile duct stone	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Immune system disorders Anti-neutrophil cytoplasmic antibody positive vasculitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Abdominal sepsis	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Arthritis bacterial	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Asymptomatic COVID-19	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Atypical pneumonia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Bacteraemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Bronchiolitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Bronchitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Bronchopulmonary aspergillosis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations COVID-19	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Carbuncle	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Cellulitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 9/278 • Number of events 13 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Cerebral aspergillosis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Clostridium difficile colitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Complicated appendicitis	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Diabetic foot infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Diverticulitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Encephalitis fungal	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Epstein-Barr viraemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Escherichia sepsis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Gastroenteritis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Gastroenteritis norovirus	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Gastroenteritis viral	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations H1N1 influenza	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Haemophilus infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Haemophilus sepsis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Hepatitis viral	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Herpes simplex viraemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Herpes zoster	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Herpes zoster disseminated	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Herpes zoster meningoencephalitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Herpes zoster oticus	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Kidney infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Listeria sepsis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Localised infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Lower respiratory tract infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Lower respiratory tract infection viral	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Mastoiditis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Meningitis cryptococcal	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Meningitis streptococcal	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Otitis externa	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Parainfluenzae virus infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Pneumonia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 8 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	9.4% 26/278 • Number of events 28 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.3% 6/95 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Pneumonia cryptococcal	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Pneumonia influenzal	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Pneumonia staphylococcal	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Pneumonia streptococcal	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Pneumonia viral	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Postoperative wound infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Pseudomonal sepsis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Pulmonary sepsis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Pyelonephritis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Respiratory syncytial virus infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Respiratory tract infection viral	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Rhinovirus infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Scedosporium infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Scrotal infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Sepsis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.4% 4/278 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Septic shock	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Sinusitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Skin infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Staphylococcal abscess	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Streptococcal bacteraemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Subcutaneous abscess	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Systemic viral infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Upper respiratory tract infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Urinary tract infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.3% 12/278 • Number of events 15 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Vestibular neuronitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Viral infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Wound infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Contusion	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Fall	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Joint injury	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Post procedural fever	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Transfusion reaction	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Ulna fracture	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Investigations Neutrophil count decreased	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Fluid overload	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Gout	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Tumour lysis syndrome	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Haemarthrosis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Soft tissue necrosis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) External ear neoplasm malignant	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal papillary mucinous neoplasm	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lentigo maligna	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma metastatic	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Sarcomatoid carcinoma of the lung	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin squamous cell carcinoma recurrent	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of head and neck	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the parotid gland	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Central nervous system lesion	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Cerebral infarction	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Depressed level of consciousness	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Embolic stroke	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Haemorrhage intracranial	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Headache	33.3% 1/3 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Hypoglossal nerve paralysis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Lethargy	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Sciatica	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Syncope	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Transient ischaemic attack	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Psychiatric disorders Anxiety	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Psychiatric disorders Bipolar disorder	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Psychiatric disorders Chronic idiopathic pain syndrome	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Psychiatric disorders Delirium	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Psychiatric disorders Delirium tremens	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Psychiatric disorders Delusional disorder, unspecified type	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.4% 4/278 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Calculus bladder	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Cystitis haemorrhagic	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Haematuria	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.4% 4/278 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Hydronephrosis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Renal artery thrombosis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Renal colic	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Subcapsular renal haematoma	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Reproductive system and breast disorders Pelvic pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Organising pneumonia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.8% 5/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Diabetic foot	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Purpura	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Vascular disorders Haematoma	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Vascular disorders Hypertension	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Vascular disorders Lymphoedema	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Vascular disorders Orthostatic hypotension	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Vascular disorders Vasculitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.

Other adverse events

Other adverse events
Measure	Part 1: 40 mg QD n=3 participants at risk Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 80 mg QD n=4 participants at risk Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1: 160 mg QD n=5 participants at risk Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up	Part 1 and Part 2: 160 mg BID n=278 participants at risk Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.	Part 1 and Part 2: 320 mg QD n=95 participants at risk Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.
Eye disorders Cataract	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.8% 5/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.3% 5/95 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Eye disorders Dry eye	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Eye disorders Lacrimation increased	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Peripheral swelling	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.0% 11/278 • Number of events 12 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.3% 6/95 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Tinea pedis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Tooth abscess	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	60.0% 3/5 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	14.0% 39/278 • Number of events 64 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	8.4% 8/95 • Number of events 16 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Blood and lymphatic system disorders Increased tendency to bruise	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.2% 6/278 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	7.4% 7/95 • Number of events 7 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	15.8% 44/278 • Number of events 107 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	10.5% 10/95 • Number of events 29 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Blood and lymphatic system disorders Spontaneous haemorrhage	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	9.0% 25/278 • Number of events 42 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Atrial fibrillation	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.7% 13/278 • Number of events 15 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Bradycardia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Cardiac failure congestive	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Palpitations	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 9/278 • Number of events 10 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Pericardial effusion	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Cardiac disorders Right ventricular failure	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Ear and labyrinth disorders Ear pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.8% 5/278 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Ear and labyrinth disorders Tinnitus	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Ear and labyrinth disorders Vertigo	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.7% 13/278 • Number of events 14 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Eye disorders Blepharitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Eye disorders Ocular rosacea	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Eye disorders Periorbital oedema	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Eye disorders Vision blurred	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Eye disorders Visual impairment	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Abdominal distension	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.8% 5/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	7.6% 21/278 • Number of events 24 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	8.4% 8/95 • Number of events 11 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 9/278 • Number of events 15 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	18.0% 50/278 • Number of events 59 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	24.2% 23/95 • Number of events 29 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Dental caries	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Diarrhoea	66.7% 2/3 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	50.0% 2/4 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	27.7% 77/278 • Number of events 122 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	24.2% 23/95 • Number of events 36 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Dyspepsia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.5% 7/278 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Gastrooesophageal reflux disease	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	8.6% 24/278 • Number of events 27 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	8.4% 8/95 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Inguinal hernia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Mouth haemorrhage	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Mouth ulceration	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.9% 8/278 • Number of events 8 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Nausea	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	50.0% 2/4 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	16.2% 45/278 • Number of events 55 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	18.9% 18/95 • Number of events 32 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Stomatitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.6% 10/278 • Number of events 10 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Toothache	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.8% 5/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.3% 5/95 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	50.0% 2/4 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	10.4% 29/278 • Number of events 38 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.3% 6/95 • Number of events 8 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Asthenia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.3% 12/278 • Number of events 20 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Fatigue	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	17.6% 49/278 • Number of events 55 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	27.4% 26/95 • Number of events 33 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Influenza like illness	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.0% 14/278 • Number of events 17 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	11.6% 11/95 • Number of events 11 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Oedema peripheral	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	11.2% 31/278 • Number of events 35 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	8.4% 8/95 • Number of events 14 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.0% 11/278 • Number of events 13 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Pyrexia	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	50.0% 2/4 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	12.9% 36/278 • Number of events 85 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.3% 5/95 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
General disorders Sensation of foreign body	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Immune system disorders Hypogammaglobulinaemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.6% 10/278 • Number of events 11 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Immune system disorders Seasonal allergy	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Bronchitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.6% 10/278 • Number of events 11 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.3% 5/95 • Number of events 8 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Cat scratch disease	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Cellulitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.5% 18/278 • Number of events 25 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	11.6% 11/95 • Number of events 15 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Chest wall abscess	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Conjunctivitis	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.0% 14/278 • Number of events 14 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.3% 5/95 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Diverticulitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Ear infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.9% 8/278 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 7 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Folliculitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.4% 4/278 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Gastroenteritis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.2% 6/278 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Helicobacter infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Herpes simplex reactivation	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Herpes zoster	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.7% 13/278 • Number of events 15 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.3% 6/95 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Influenza	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 9/278 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Localised infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.7% 13/278 • Number of events 21 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	9.5% 9/95 • Number of events 10 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Lower respiratory tract infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	8.3% 23/278 • Number of events 41 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	8.4% 8/95 • Number of events 11 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Nasal herpes	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Nasopharyngitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	7.9% 22/278 • Number of events 32 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	7.4% 7/95 • Number of events 11 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Onychomycosis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Ophthalmic herpes zoster	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Oral candidiasis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Oral herpes	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.1% 17/278 • Number of events 22 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Pneumonia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	7.9% 22/278 • Number of events 24 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	7.4% 7/95 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Pneumonia bacterial	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Sinusitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	12.2% 34/278 • Number of events 48 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	8.4% 8/95 • Number of events 14 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Skin infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.7% 13/278 • Number of events 18 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.3% 6/95 • Number of events 7 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Upper respiratory tract infection	66.7% 2/3 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	50.0% 2/4 • Number of events 7 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	40.0% 2/5 • Number of events 10 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	38.1% 106/278 • Number of events 214 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	48.4% 46/95 • Number of events 89 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Urinary tract infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	15.8% 44/278 • Number of events 70 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	18.9% 18/95 • Number of events 31 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.8% 5/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Arthropod bite	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Chest injury	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Contusion	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	40.0% 2/5 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	34.9% 97/278 • Number of events 135 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	41.1% 39/95 • Number of events 57 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Fall	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	10.1% 28/278 • Number of events 38 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	9.5% 9/95 • Number of events 13 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Limb injury	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.5% 7/278 • Number of events 7 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	9.5% 9/95 • Number of events 10 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Post procedural contusion	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.4% 4/278 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.3% 12/278 • Number of events 12 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.3% 5/95 • Number of events 7 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.3% 12/278 • Number of events 16 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	9.5% 9/95 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Investigations Alanine aminotransferase increased	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.6% 10/278 • Number of events 13 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 8 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Investigations Blood creatinine increased	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.6% 10/278 • Number of events 11 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Investigations Gamma-glutamyltransferase increased	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Investigations International normalised ratio increased	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Investigations Neutrophil count decreased	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.5% 18/278 • Number of events 93 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 8 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Investigations Platelet count decreased	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.1% 17/278 • Number of events 28 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Investigations Serum ferritin decreased	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Investigations Weight decreased	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	8.3% 23/278 • Number of events 25 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.3% 6/95 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.5% 18/278 • Number of events 27 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.5% 7/278 • Number of events 10 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Iron deficiency	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.4% 4/278 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Metabolism and nutrition disorders Vitamin B12 deficiency	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Arthralgia	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	13.3% 37/278 • Number of events 54 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	13.7% 13/95 • Number of events 15 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 9/278 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	75.0% 3/4 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	12.2% 34/278 • Number of events 38 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	24.2% 23/95 • Number of events 28 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.8% 5/278 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.2% 6/278 • Number of events 8 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.3% 5/95 • Number of events 7 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	9.0% 25/278 • Number of events 29 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	12.6% 12/95 • Number of events 13 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.5% 7/278 • Number of events 7 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.5% 7/278 • Number of events 7 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.7% 13/278 • Number of events 15 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.3% 6/95 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.1% 17/278 • Number of events 19 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	7.4% 7/95 • Number of events 11 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.0% 11/278 • Number of events 13 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.8% 5/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.5% 18/278 • Number of events 25 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	10.5% 10/95 • Number of events 11 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Musculoskeletal and connective tissue disorders Sacroiliitis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Angiomyolipoma	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	7.9% 22/278 • Number of events 45 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	9.5% 9/95 • Number of events 16 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign ear neoplasm	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cutaneous T-cell lymphoma	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin cancer	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.1% 17/278 • Number of events 23 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.3% 5/95 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Burning sensation	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Cognitive disorder	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Dizziness	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	10.1% 28/278 • Number of events 35 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	11.6% 11/95 • Number of events 16 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Headache	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	50.0% 2/4 • Number of events 7 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	40.0% 2/5 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	16.5% 46/278 • Number of events 63 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	18.9% 18/95 • Number of events 21 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Lethargy	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.2% 6/278 • Number of events 7 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Memory impairment	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Paraesthesia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.7% 13/278 • Number of events 14 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.3% 6/95 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Peripheral sensory neuropathy	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.8% 16/278 • Number of events 19 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Post herpetic neuralgia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Sciatica	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Nervous system disorders Somnolence	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Psychiatric disorders Depressed mood	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Psychiatric disorders Depression	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.4% 4/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Psychiatric disorders Hallucination	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Psychiatric disorders Insomnia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.5% 18/278 • Number of events 19 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.3% 5/95 • Number of events 7 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Dysuria	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.8% 5/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.2% 4/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Haematuria	33.3% 1/3 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	11.2% 31/278 • Number of events 39 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	12.6% 12/95 • Number of events 15 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Pollakiuria	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.8% 5/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	8.4% 8/95 • Number of events 8 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Renal colic	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Urinary hesitation	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Renal and urinary disorders Urinary incontinence	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.72% 2/278 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Cough	66.7% 2/3 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	28.4% 79/278 • Number of events 101 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	22.1% 21/95 • Number of events 24 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Dysphonia	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.8% 5/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	8.6% 24/278 • Number of events 30 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	10.5% 10/95 • Number of events 18 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 9/278 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	9.7% 27/278 • Number of events 44 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	10.5% 10/95 • Number of events 14 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.0% 14/278 • Number of events 16 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.8% 19/278 • Number of events 27 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.3% 5/95 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Pleural effusion	33.3% 1/3 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.2% 6/278 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.8% 19/278 • Number of events 27 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/278 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 9/278 • Number of events 10 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.9% 8/278 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.3% 5/95 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Sinus pain	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.2% 6/278 • Number of events 6 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.6% 10/278 • Number of events 14 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Respiratory, thoracic and mediastinal disorders Wheezing	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Actinic keratosis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.5% 7/278 • Number of events 9 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.3% 5/95 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.4% 4/278 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Blood blister	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.3% 12/278 • Number of events 15 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.5% 7/278 • Number of events 7 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.3% 5/95 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.0% 11/278 • Number of events 13 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.6% 10/278 • Number of events 12 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Petechiae	33.3% 1/3 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	7.9% 22/278 • Number of events 24 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	9.5% 9/95 • Number of events 12 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	40.0% 2/5 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	9.7% 27/278 • Number of events 31 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	10.5% 10/95 • Number of events 11 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Purpura	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.9% 8/278 • Number of events 10 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 3/95 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.1% 56/278 • Number of events 78 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	21.1% 20/95 • Number of events 28 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Rash erythematous	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 3/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/95 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.8% 5/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	3.2% 9/278 • Number of events 12 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	2.1% 2/95 • Number of events 4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.4% 4/278 • Number of events 5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	6.3% 6/95 • Number of events 7 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Rosacea	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	40.0% 2/5 • Number of events 2 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	5.4% 15/278 • Number of events 17 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	7.4% 7/95 • Number of events 8 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Vascular disorders Hypertension	33.3% 1/3 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	25.0% 1/4 • Number of events 3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	13.3% 37/278 • Number of events 56 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	11.6% 11/95 • Number of events 15 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Vascular disorders Hypotension	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/5 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	4.0% 11/278 • Number of events 12 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.
Vascular disorders Peripheral venous disease	0.00% 0/3 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.00% 0/4 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	20.0% 1/5 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	0.36% 1/278 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.	1.1% 1/95 • Number of events 1 • Up to 6 years and 7 months One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.

Additional Information

Study Director

BeiGene

Phone: 1-877-828-5568

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information \& may request a further delay to protect its IP rights.
Publication restrictions are in place

Restriction type: OTHER