Trial Outcomes & Findings for Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF (NCT NCT02101268)

Last Updated: 2023-05-23

Results Overview

Splenic response rate at Week 24 is defined as the percentage of participants who achieved a spleen volume reduction of ≥ 35% from baseline at the Week 24 assessment as measured by MRI or CT.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

156 participants

Primary outcome timeframe

Week 24

Results posted on

2023-05-23

Participant Flow

156 participants were randomized at 52 centers in 8 countries.

Participants were screened within 30 days before randomization to determine eligibility for participation in the study. Participants who were not randomized within the 30-day screening window were considered screen failures. At randomization, participants were randomly assigned 2:1 to MMB:BAT.

Participant milestones

Participant milestones
Measure	Momelotinib (MMB) Participants received momelotinib orally once daily at a starting dose of 200 mg. Additional available strengths included 100 mg and 150 mg.	Best Available Therapy (BAT) Participants received treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may have been changed at any time during the study except during the screening period. No active therapy was a permissible option.	MMB to MMB After completion of the 24-week randomized treatment phase, participants randomized to the MMB group who tolerated and derived clinical benefit from MMB had the option to receive MMB at their current dose in an extended treatment phase for up to an additional 204 weeks. Available strengths included 100 mg, 150 mg and 200 mg.	BAT to MMB After completion of the 24-week randomized treatment phase, participants randomized to the BAT treatment arm had the option to receive MMB 200 mg once daily in an extended treatment phase for up to an additional 204 weeks. Additional available strengths included 100 mg and 150 mg.
Randomized Treatment Phase STARTED	104	52	0	0
Randomized Treatment Phase COMPLETED	77	41	0	0
Randomized Treatment Phase NOT COMPLETED	27	11	0	0
Extended Treatment Phase STARTED	0	0	64	40
Extended Treatment Phase COMPLETED	0	0	0	0
Extended Treatment Phase NOT COMPLETED	0	0	64	40

Reasons for withdrawal

Reasons for withdrawal
Measure	Momelotinib (MMB) Participants received momelotinib orally once daily at a starting dose of 200 mg. Additional available strengths included 100 mg and 150 mg.	Best Available Therapy (BAT) Participants received treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may have been changed at any time during the study except during the screening period. No active therapy was a permissible option.	MMB to MMB After completion of the 24-week randomized treatment phase, participants randomized to the MMB group who tolerated and derived clinical benefit from MMB had the option to receive MMB at their current dose in an extended treatment phase for up to an additional 204 weeks. Available strengths included 100 mg, 150 mg and 200 mg.	BAT to MMB After completion of the 24-week randomized treatment phase, participants randomized to the BAT treatment arm had the option to receive MMB 200 mg once daily in an extended treatment phase for up to an additional 204 weeks. Additional available strengths included 100 mg and 150 mg.
Randomized Treatment Phase Subject Decision	8	4	0	0
Randomized Treatment Phase Physician Decision	4	1	0	0
Randomized Treatment Phase Symptomatic Spleen Growth	0	1	0	0
Randomized Treatment Phase Adverse Event	6	0	0	0
Randomized Treatment Phase Death	5	4	0	0
Randomized Treatment Phase Disease Progression	4	1	0	0
Extended Treatment Phase Subject Decision	0	0	3	2
Extended Treatment Phase Physician Decision	0	0	5	2
Extended Treatment Phase Adverse Event	0	0	14	18
Extended Treatment Phase Death	0	0	5	1
Extended Treatment Phase Transferred to Study SRA-MMB-4365	0	0	15	7
Extended Treatment Phase Disease Progression	0	0	13	6
Extended Treatment Phase Lack of Efficacy	0	0	9	4

Baseline Characteristics

Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Momelotinib (MMB) n=104 Participants Participants received momelotinib orally once daily at a starting dose of 200 mg. Additional available strengths included 100 mg and 150 mg.	Best Available Therapy (BAT) n=52 Participants Participants received treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may have been changed at any time during the study except during the screening period. No active therapy was a permissible option.	Total n=156 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	41 Participants n=5 Participants	14 Participants n=7 Participants	55 Participants n=5 Participants
Age, Categorical >=65 years	63 Participants n=5 Participants	38 Participants n=7 Participants	101 Participants n=5 Participants
Age, Continuous	67.0 years n=5 Participants	69.5 years n=7 Participants	68.0 years n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	28 Participants n=7 Participants	63 Participants n=5 Participants
Sex: Female, Male Male	69 Participants n=5 Participants	24 Participants n=7 Participants	93 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	81 Participants n=5 Participants	40 Participants n=7 Participants	121 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	18 Participants n=5 Participants	8 Participants n=7 Participants	26 Participants n=5 Participants
Race/Ethnicity, Customized White	83 Participants n=5 Participants	44 Participants n=7 Participants	127 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Not Permitted	15 Participants n=5 Participants	8 Participants n=7 Participants	23 Participants n=5 Participants
Transfusion Dependent Yes	58 Participants n=5 Participants	27 Participants n=7 Participants	85 Participants n=5 Participants
Transfusion Dependent No	46 Participants n=5 Participants	25 Participants n=7 Participants	71 Participants n=5 Participants
Total Symptom Score (TSS) < 18	61 Participants n=5 Participants	28 Participants n=7 Participants	89 Participants n=5 Participants
Total Symptom Score (TSS) >= 18	43 Participants n=5 Participants	24 Participants n=7 Participants	67 Participants n=5 Participants
Weight	75.4 kg n=5 Participants	74.0 kg n=7 Participants	75.0 kg n=5 Participants
Height	170.0 cm n=5 Participants	168.0 cm n=7 Participants	170.0 cm n=5 Participants
Body Mass Index	25.9 kg/m^2 n=5 Participants	26.1 kg/m^2 n=7 Participants	26.0 kg/m^2 n=5 Participants
Hemoglobin	9.0 g/dL n=5 Participants	9.2 g/dL n=7 Participants	9.0 g/dL n=5 Participants

PRIMARY outcome

Timeframe: Week 24

Splenic response rate at Week 24 is defined as the percentage of participants who achieved a spleen volume reduction of ≥ 35% from baseline at the Week 24 assessment as measured by MRI or CT.

Outcome measures

Outcome measures
Measure	Momelotinib (MMB) n=104 Participants Participants received momelotinib orally once daily at a starting dose of 200 mg. Additional available strengths included 100 mg and 150 mg.	Best Available Therapy (BAT) n=52 Participants Participants received treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may have been changed at any time during the study except during the screening period. No active therapy was a permissible option.
Splenic Response Rate at Week 24 Responder	7 Participants	3 Participants
Splenic Response Rate at Week 24 Nonresponder	97 Participants	49 Participants

SECONDARY outcome

Timeframe: Week 24

Population: TSS rate analysis at Week 24 only included participants with TSS \> 0 at baseline or with TSS = 0 at baseline but with TSS \> 0 or missing at Week 24.

Total symptom score (TSS) is defined as the percentage of participants who achieved a ≥50% reduction in TSS at Week 24 versus baseline as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) v2.0 diary. Response rate was calculated using the average of the daily TSS from a consecutive 28-day period prior to Week 24, which had ≥20 daily TSS available. The modified MPN-SAF patient-reported outcome instrument consisted of 8 items assessing worst daily incidence of tiredness, filling up quickly, abdominal discomfort, night sweats, itching, bone pain, pain under ribs on left side, and inactivity. Scoring of TSS in this study was based on 7 of these items, (0-70) excluding inactivity. These items assess the impact experienced by the participant in the 24 hours prior to completing the questionnaire. All items are measured using a 0 to 10 Numeric Rating Scale, with 0 corresponding to "Absent" and 10 corresponding to "Worst Imaginable."

Outcome measures

Outcome measures
Measure	Momelotinib (MMB) n=103 Participants Participants received momelotinib orally once daily at a starting dose of 200 mg. Additional available strengths included 100 mg and 150 mg.	Best Available Therapy (BAT) n=51 Participants Participants received treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may have been changed at any time during the study except during the screening period. No active therapy was a permissible option.
Total Symptom Score (TSS) Response Rate at Week 24 Responder	27 Participants	3 Participants
Total Symptom Score (TSS) Response Rate at Week 24 Nonresponder	76 Participants	48 Participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Rate of RBC transfusion is defined as the average number of RBC units transfused not associated with clinically overt bleeding per subject-month during the randomized treatment Phase.

Outcome measures

Outcome measures
Measure	Momelotinib (MMB) n=104 Participants Participants received momelotinib orally once daily at a starting dose of 200 mg. Additional available strengths included 100 mg and 150 mg.	Best Available Therapy (BAT) n=52 Participants Participants received treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may have been changed at any time during the study except during the screening period. No active therapy was a permissible option.
Rate of Red Blood Cell (RBC) Transfusion in the Randomized Treatment Phase, (the Average Number of RBC Units Transfused Per Month Not Associated With Overt Bleeding)	0.5 units/month Interval 0.0 to 2.4	1.2 units/month Interval 0.0 to 2.8

SECONDARY outcome

Timeframe: Week 24

RBC transfusion independence rate is the percentage of participants who achieved transfusion independence at Week 24 (responders). RBC transfusion independence is defined as absence of RBC transfusions and no hemoglobin level below 8 g/dL in the 12 weeks prior to Week 24, excluding cases associated with clinically overt bleeding. Transfusion dependence, (non-responder) is defined as at least 4 units of RBC transfusion, or a Hgb level below 8 g/dL, in the 8 weeks prior to week 24. Methods used to assess this outcome measure include collection and recording of any instances of RBC transfusions and collection and recording of any local or central lab hemoglobin measurements

Outcome measures

Outcome measures
Measure	Momelotinib (MMB) n=104 Participants Participants received momelotinib orally once daily at a starting dose of 200 mg. Additional available strengths included 100 mg and 150 mg.	Best Available Therapy (BAT) n=52 Participants Participants received treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may have been changed at any time during the study except during the screening period. No active therapy was a permissible option.
RBC Transfusion Independence Rate at Week 24, (Defined as Absence of RBC Transfusions and no Hemoglobin Level Below 8 g/dL in the 12 Weeks Prior to Week 24, Excluding Cases Associated With Clinically Overt Bleeding) Responder	45 Participants	11 Participants
RBC Transfusion Independence Rate at Week 24, (Defined as Absence of RBC Transfusions and no Hemoglobin Level Below 8 g/dL in the 12 Weeks Prior to Week 24, Excluding Cases Associated With Clinically Overt Bleeding) Nonresponder	59 Participants	41 Participants

SECONDARY outcome

Timeframe: Week 24

RBC transfusion dependence is the percentage of participants who are transfusion dependent at Week 24, defined as at least 4 units of RBC transfusions, or a hemoglobin level below 8 g/dL in the 8 weeks prior to Week 24, excluding cases associated with clinically overt bleeding.

Outcome measures

Outcome measures
Measure	Momelotinib (MMB) n=104 Participants Participants received momelotinib orally once daily at a starting dose of 200 mg. Additional available strengths included 100 mg and 150 mg.	Best Available Therapy (BAT) n=52 Participants Participants received treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may have been changed at any time during the study except during the screening period. No active therapy was a permissible option.
RBC Transfusion Dependence Rate at Week 24 Dependent	52 Participants	33 Participants
RBC Transfusion Dependence Rate at Week 24 Nondependent	52 Participants	19 Participants

Adverse Events

Momelotinib (MMB)

Serious events: 37 serious events

Other events: 99 other events

Deaths: 8 deaths

Best Available Therapy (BAT)

Serious events: 12 serious events

Other events: 46 other events

Deaths: 5 deaths

MMB to MMB

Serious events: 33 serious events

Other events: 63 other events

Deaths: 29 deaths

BAT to MMB

Serious events: 19 serious events

Other events: 40 other events

Deaths: 18 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

Sierra Oncology, a GlaxoSmithKline company

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Agreements varied with individual investigators, but did not prohibit any investigator from publishing. Investigators were not to publish results of the study until a period of time (eg. 2 years) following completion of the trial at all participating institutions but could do so earlier with consent of the Sponsor.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Momelotinib (MMB) n=104 participants at risk Participants received momelotinib orally once daily at a starting dose of 200 mg. Additional available strengths included 100 mg and 150 mg.	Best Available Therapy (BAT) n=52 participants at risk Participants received treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may have been changed at any time during the study except during the screening period. No active therapy was a permissible option.	MMB to MMB n=64 participants at risk After completion of the 24-week randomized treatment phase, participants randomized to the MMB group who tolerated and derived clinical benefit from MMB had the option to receive MMB at their current dose in an extended treatment phase for up to an additional 204 weeks. Available strengths included 100 mg, 150 mg and 200 mg.	BAT to MMB n=40 participants at risk After completion of the 24-week randomized treatment phase, participants randomized to the BAT treatment arm had the option to receive MMB 200 mg once daily in an extended treatment phase for up to an additional 204 weeks. Additional available strengths included 100 mg and 150 mg.
Infections and infestations Cellulitis	1.9% 2/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Pneumonia	1.9% 2/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.9% 1/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	9.4% 6/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Sepsis	1.9% 2/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	3.8% 2/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	6.2% 4/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Bacterial sepsis	0.96% 1/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Diverticulitis	0.96% 1/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Enterobacter bacteraemia	0.96% 1/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Lung infection	0.96% 1/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Ophthalmic herpes zoster	0.96% 1/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Peritonitis bacterial	0.96% 1/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Sinusitis	0.96% 1/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Upper respiratory tract infection	0.96% 1/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Clostridium difficile infection	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Device related sepsis	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.9% 1/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Gastroenteritis	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.9% 1/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Herpes zoster	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.9% 1/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Lower respiratory tract infection	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.9% 1/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Urosepsis	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Bronchitis	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Bacteraemia	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Escherichia bacteraemia	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Infection	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Influenza	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Otitis media	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Pneumonia viral	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Soft tissue infection	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Urinary tract infection	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Cardiac disorders Cardiac failure	2.9% 3/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.9% 1/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	5.0% 2/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Cardiac disorders Supraventricular tachycardia	1.9% 2/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Cardiac disorders Angina unstable	0.96% 1/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Cardiac disorders Atrial fibrillation	0.96% 1/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Cardiac disorders Cardiac arrest	0.96% 1/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Cardiac disorders Cardiac failure congestive	0.96% 1/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Cardiac disorders Left ventricular failure	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Cardiac disorders Myocardial infarction	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Cardiac disorders Myocardial ischaemia	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Cardiac disorders Tachycardia	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.9% 1/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Cardiac disorders Acute myocardial infarction	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Cardiac disorders Cardiac failure acute	0.00% 0/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.6% 1/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.9% 2/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	3.1% 2/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.9% 2/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.

Other adverse events
Measure	Momelotinib (MMB) n=104 participants at risk Participants received momelotinib orally once daily at a starting dose of 200 mg. Additional available strengths included 100 mg and 150 mg.	Best Available Therapy (BAT) n=52 participants at risk Participants received treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may have been changed at any time during the study except during the screening period. No active therapy was a permissible option.	MMB to MMB n=64 participants at risk After completion of the 24-week randomized treatment phase, participants randomized to the MMB group who tolerated and derived clinical benefit from MMB had the option to receive MMB at their current dose in an extended treatment phase for up to an additional 204 weeks. Available strengths included 100 mg, 150 mg and 200 mg.	BAT to MMB n=40 participants at risk After completion of the 24-week randomized treatment phase, participants randomized to the BAT treatment arm had the option to receive MMB 200 mg once daily in an extended treatment phase for up to an additional 204 weeks. Additional available strengths included 100 mg and 150 mg.
Gastrointestinal disorders Diarrhoea	31.7% 33/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	15.4% 8/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	29.7% 19/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	25.0% 10/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Respiratory, thoracic and mediastinal disorders Cough	17.3% 18/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	11.5% 6/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	26.6% 17/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	20.0% 8/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
General disorders Asthenia	19.2% 20/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	21.2% 11/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	12.5% 8/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	27.5% 11/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
General disorders Pyrexia	12.5% 13/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.7% 4/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	25.0% 16/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	25.0% 10/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Blood and lymphatic system disorders Thrombocytopenia	17.3% 18/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	11.5% 6/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	12.5% 8/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	27.5% 11/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Gastrointestinal disorders Nausea	19.2% 20/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	9.6% 5/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	12.5% 8/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	12.5% 5/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Blood and lymphatic system disorders Anaemia	14.4% 15/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	19.2% 10/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	21.9% 14/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	15.0% 6/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
General disorders Fatigue	15.4% 16/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	19.2% 10/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	10.9% 7/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	17.5% 7/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Gastrointestinal disorders Abdominal pain	15.4% 16/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	13.5% 7/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	10.9% 7/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	12.5% 5/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
General disorders Oedema peripheral	10.6% 11/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	11.5% 6/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	15.6% 10/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	15.0% 6/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Nervous system disorders Dizziness	15.4% 16/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.7% 4/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	9.4% 6/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	15.0% 6/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Nervous system disorders Headache	15.4% 16/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	5.8% 3/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	6.2% 4/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	15.0% 6/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Urinary tract infection	10.6% 11/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.7% 4/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	12.5% 8/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	20.0% 8/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.5% 12/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	13.5% 7/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.8% 5/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	15.0% 6/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Skin and subcutaneous tissue disorders Pruritus	12.5% 13/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.7% 4/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	12.5% 8/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.5% 3/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Upper respiratory tract infection	8.7% 9/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	5.8% 3/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	12.5% 8/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	12.5% 5/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Investigations Weight decreased	9.6% 10/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	5.8% 3/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	10.9% 7/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	12.5% 5/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Nervous system disorders Peripheral sensory neuropathy	6.7% 7/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	9.4% 6/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	17.5% 7/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Gastrointestinal disorders Constipation	10.6% 11/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	3.8% 2/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.8% 5/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Skin and subcutaneous tissue disorders Night sweats	7.7% 8/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.7% 4/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	4.7% 3/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	15.0% 6/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Metabolism and nutrition disorders Decreased appetite	6.7% 7/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	3.8% 2/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	6.2% 4/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	12.5% 5/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Musculoskeletal and connective tissue disorders Arthralgia	9.6% 10/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.7% 4/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	9.4% 6/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Musculoskeletal and connective tissue disorders Back pain	4.8% 5/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.7% 4/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	14.1% 9/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.5% 3/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Infections and infestations Bronchitis	4.8% 5/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	3.8% 2/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	9.4% 6/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	10.0% 4/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Metabolism and nutrition disorders Hyperkalaemia	7.7% 8/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.9% 1/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.8% 5/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	5.0% 2/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Vascular disorders Hypertension	9.6% 10/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	3.8% 2/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.8% 5/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	5.0% 2/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Nervous system disorders Paraesthesia	7.7% 8/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.9% 1/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	6.2% 4/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.5% 3/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Gastrointestinal disorders Vomiting	6.7% 7/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.9% 1/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.8% 5/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	10.0% 4/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Gastrointestinal disorders Abdominal pain upper	7.7% 8/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.9% 1/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	3.1% 2/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	10.0% 4/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Metabolism and nutrition disorders Hyperuricaemia	5.8% 6/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	3.8% 2/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	6.2% 4/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.5% 3/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Musculoskeletal and connective tissue disorders Pain in extremity	4.8% 5/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	9.6% 5/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	10.9% 7/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Gastrointestinal disorders Dyspepsia	9.6% 10/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.9% 1/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	3.1% 2/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Metabolism and nutrition disorders Vitamin B1 deficiency	6.7% 7/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	3.8% 2/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	9.4% 6/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Investigations Blood creatinine increased	5.8% 6/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	6.2% 4/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	2.5% 1/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.7% 8/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	11.5% 6/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	3.1% 2/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	5.0% 2/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Metabolism and nutrition disorders Hypokalaemia	3.8% 4/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	0.00% 0/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	4.7% 3/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	10.0% 4/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Blood and lymphatic system disorders Neutropenia	6.7% 7/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.9% 1/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	3.1% 2/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.5% 3/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Skin and subcutaneous tissue disorders Hyperhidrosis	4.8% 5/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	9.6% 5/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	4.7% 3/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	5.0% 2/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Psychiatric disorders Insomnia	2.9% 3/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.7% 4/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	6.2% 4/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.5% 3/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.
Musculoskeletal and connective tissue disorders Muscle spasms	2.9% 3/104 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	1.9% 1/52 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	7.8% 5/64 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.	5.0% 2/40 • Serious and other Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship. Serious events are monitored up to 12 weeks and all-cause mortality was assessed for up to 5 years.