Trial Outcomes & Findings for A Study to Assess the Effectiveness and Safety of Irinotecan Liposome Injection, 5-fluorouracil/Leucovorin Plus Oxaliplatin in Patients Not Previously Treated for Metastatic Pancreatic Cancer, Compared to Nab-paclitaxel+Gemcitabine Treatment (NCT NCT04083235)

NCT ID: NCT04083235

Last Updated: 2025-02-27

Results Overview

The OS was defined as time from the date of randomization to the date of death due to any cause. Participants who did not have a date of death recorded at the time of the final analysis were censored at the last known time that the participant was alive. The median OS was measured using Kaplan-Meier technique.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 770 participants
• Primary outcome timeframe: Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, end of treatment (EoT) visit, then every 2 months thereafter up to DCO date of 23 July 2022 (maximum of 893 days)
• Results posted on: 2025-02-27

Participant Flow

This Phase 3, open-label study was conducted in participants with metastatic adenocarcinoma of the pancreas at 187 investigational sites in 18 countries (Australia, Brazil, Canada, Israel, Republic of Korea, United States, Austria, Belgium, Czechia, France, Germany, Greece, Hungary, Italy, Portugal, Spain, United Kingdom, and Russia). First participant was recruited on 11 February 2020 and data cut-off (DCO) date was 23 July 2022.

This study consisted of a screening period (up to 28 days), treatment period (28-day cycles of treatment until radiologically determined disease progression per response evaluation criteria in solid tumors [RECIST 1.1]), unacceptable study medication related toxicity or withdrawal from study treatment followed by survival follow-up (until death or study closure, whichever occurred first). A total of 770 participants were randomized in 1:1 ratio using an interactive web response system (IWRS).

Participant milestones

Measure	NALIRIFOX Participants were treated with irinotecan liposome injection 50 milligram per square meter (mg/m\^2) followed by oxaliplatin 60 mg/m\^2, followed by leucovorin (LV) 400 mg/m\^2 and then 5-fluorouracil (FU) 2400 mg/m\^2 intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.	Nab-paclitaxel+Gemcitabine Participants were treated with nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 IV on Days 1, 8 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
Overall Study STARTED	383	387
Overall Study Received Treatment	370	379
Overall Study COMPLETED	59	77
Overall Study NOT COMPLETED	324	310

Reasons for withdrawal

Measure	NALIRIFOX Participants were treated with irinotecan liposome injection 50 milligram per square meter (mg/m\^2) followed by oxaliplatin 60 mg/m\^2, followed by leucovorin (LV) 400 mg/m\^2 and then 5-fluorouracil (FU) 2400 mg/m\^2 intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.	Nab-paclitaxel+Gemcitabine Participants were treated with nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 IV on Days 1, 8 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
Overall Study Death	252	277
Overall Study Withdrawal by Subject	13	17
Overall Study Lost to Follow-up	1	1
Overall Study Does not meet entry criteria	1	0
Overall Study Did not receive treatment	13	8
Overall Study Ongoing at the time of DCO	44	7

Baseline Characteristics

A Study to Assess the Effectiveness and Safety of Irinotecan Liposome Injection, 5-fluorouracil/Leucovorin Plus Oxaliplatin in Patients Not Previously Treated for Metastatic Pancreatic Cancer, Compared to Nab-paclitaxel+Gemcitabine Treatment

Baseline characteristics by cohort

Measure	NALIRIFOX n=383 Participants Participants were treated with irinotecan liposome injection 50 mg/m\^2 followed by oxaliplatin 60 mg/m\^2, followed by LV 400 mg/m\^2 and then 5-FU 2400 mg/m\^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.	Nab-paclitaxel+Gemcitabine n=387 Participants Participants were treated with nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 IV on Days 1, 8 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.	Total n=770 Participants Total of all reporting groups
Age, Continuous	62.8 years STANDARD_DEVIATION 9.71 • n=5 Participants	64.0 years STANDARD_DEVIATION 8.34 • n=7 Participants	63.4 years STANDARD_DEVIATION 9.06 • n=5 Participants
Sex: Female, Male Female	179 Participants n=5 Participants	157 Participants n=7 Participants	336 Participants n=5 Participants
Sex: Female, Male Male	204 Participants n=5 Participants	230 Participants n=7 Participants	434 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	49 Participants n=5 Participants	30 Participants n=7 Participants	79 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	305 Participants n=5 Participants	328 Participants n=7 Participants	633 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	29 Participants n=5 Participants	29 Participants n=7 Participants	58 Participants n=5 Participants
Race/Ethnicity, Customized White	315 Participants n=5 Participants	324 Participants n=7 Participants	639 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	26 Participants n=5 Participants	29 Participants n=7 Participants	55 Participants n=5 Participants
Race/Ethnicity, Customized Asian	20 Participants n=5 Participants	18 Participants n=7 Participants	38 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	12 Participants n=5 Participants	7 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized Other	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, end of treatment (EoT) visit, then every 2 months thereafter up to DCO date of 23 July 2022 (maximum of 893 days)

Population: The ITT population consisted of all randomized participants to whom study treatment was assigned by randomization.

The OS was defined as time from the date of randomization to the date of death due to any cause. Participants who did not have a date of death recorded at the time of the final analysis were censored at the last known time that the participant was alive. The median OS was measured using Kaplan-Meier technique.

Outcome measures

Measure	NALIRIFOX n=383 Participants Participants were treated with irinotecan liposome injection 50 mg/m\^2 followed by oxaliplatin 60 mg/m\^2, followed by LV 400 mg/m\^2 and then 5-FU 2400 mg/m\^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.	Nab-paclitaxel+Gemcitabine n=387 Participants Participants were treated with nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 IV on Days 1, 8 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
Overall Survival (OS)	11.1 months Interval 10.0 to 12.1	9.2 months Interval 8.3 to 10.6

SECONDARY outcome

Timeframe: Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose until EoT visit (maximum of 893 days)

Population: The ITT population consisted of all randomized participants to whom study treatment was assigned by randomization. Only participants with PFS event are reported.

PFS was defined as the time from the date of randomization to the first documented disease progression using response evaluation criteria in solid tumors (RECIST) Version 1.1 as per Investigator assessment or death due to any cause. The median PFS was measured using Kaplan-Meier technique.

Outcome measures

Measure	NALIRIFOX n=249 Participants Participants were treated with irinotecan liposome injection 50 mg/m\^2 followed by oxaliplatin 60 mg/m\^2, followed by LV 400 mg/m\^2 and then 5-FU 2400 mg/m\^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.	Nab-paclitaxel+Gemcitabine n=259 Participants Participants were treated with nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 IV on Days 1, 8 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
Progression Free Survival (PFS)	7.4 months Interval 6.0 to 7.7	5.6 months Interval 5.3 to 5.8

SECONDARY outcome

Timeframe: Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose until EoT visit, (maximum of 893 days)

Population: The ITT population consisted of all randomized participants to whom study treatment was assigned by randomization.

The ORR was defined as the percentage of participants with a best overall response (BOR) characterized as either a complete response (CR) or partial response (PR) per RECIST Version 1.1. BOR was defined as the best response as recorded from randomization until documented objective disease progression using RECIST Version 1.1. As per RECIST version 1.1, CR is disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. The ORR was calculated using Clopper-Pearson method.

Outcome measures

Measure	NALIRIFOX n=383 Participants Participants were treated with irinotecan liposome injection 50 mg/m\^2 followed by oxaliplatin 60 mg/m\^2, followed by LV 400 mg/m\^2 and then 5-FU 2400 mg/m\^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.	Nab-paclitaxel+Gemcitabine n=387 Participants Participants were treated with nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 IV on Days 1, 8 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
Overall Response Rate (ORR)	41.8 percentage of participants Interval 36.8 to 46.9	36.2 percentage of participants Interval 31.4 to 41.2

Adverse Events

NALIRIFOX

Serious events: 201 serious events

Other events: 364 other events

Deaths: 252 deaths

Nab-paclitaxel+Gemcitabine

Serious events: 195 serious events

Other events: 371 other events

Deaths: 277 deaths

Serious adverse events

Measure	NALIRIFOX n=370 participants at risk Participants were treated with irinotecan liposome injection 50 mg/m\^2 followed by oxaliplatin 60 mg/m\^2, followed by LV 400 mg/m\^2 and then 5-FU 2400 mg/m\^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.	Nab-paclitaxel+Gemcitabine n=379 participants at risk Participants were treated with nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 IV on Days 1, 8 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
Infections and infestations Urinary tract infection	0.81% 3/370 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	1.1% 4/379 • Number of events 4 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Asymptomatic COVID-19	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.79% 3/379 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Biliary tract infection	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Cellulitis	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.79% 3/379 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Febrile infection	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Gastroenteritis	0.81% 3/370 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Abdominal sepsis	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Bacteraemia	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Diverticulitis	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Erysipelas	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Escherichia bacteraemia	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Septic shock	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Suspected COVID-19	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Abdominal abscess	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Anal abscess	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Atypical pneumonia	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Bacterial sepsis	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Biliary sepsis	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations COVID-19 pneumonia	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Campylobacter colitis	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Catheter site infection	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Cholangitis infective	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Clostridium difficile colitis	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Device related bacteraemia	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Device related infection	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Enterococcal infection	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Gallbladder abscess	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Gastroenteritis norovirus	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Hepatic infection	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Hepatitis E	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Implant site cellulitis	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Infective spondylitis	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Large intestine infection	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Liver abscess	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Peritonitis bacterial	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Pneumonia aspiration	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Post procedural cellulitis	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Staphylococcal bacteraemia	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Streptococcal infection	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Asthenia	1.9% 7/370 • Number of events 7 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Fatigue	1.9% 7/370 • Number of events 7 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders General physical health deterioration	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	1.6% 6/379 • Number of events 6 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Malaise	0.81% 3/370 • Number of events 4 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Oedema peripheral	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.79% 3/379 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Mucosal inflammation	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Peripheral swelling	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Catheter site inflammation	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Chest pain	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Condition aggravated	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Generalised oedema	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Inadequate analgesia	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Inflammation	0.27% 1/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Multiple organ dysfunction syndrome	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Pain	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Performance status decreased	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Sudden cardiac death	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Sudden death	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Dehydration	2.7% 10/370 • Number of events 11 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	1.1% 4/379 • Number of events 4 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Hypokalaemia	1.6% 6/370 • Number of events 7 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.79% 3/379 • Number of events 4 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Decreased appetite	1.4% 5/370 • Number of events 5 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Hypoglycaemia	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	1.1% 4/379 • Number of events 5 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Hyponatraemia	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Adult failure to thrive	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Failure to thrive	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Hypophosphataemia	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Diabetic metabolic decompensation	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Electrolyte imbalance	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Hypercalcaemia	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	1.3% 5/379 • Number of events 5 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Aspiration	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Pneumonitis aspiration	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Blood and lymphatic system disorders Febrile neutropenia	1.9% 7/370 • Number of events 9 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	1.6% 6/379 • Number of events 6 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Blood and lymphatic system disorders Neutropenia	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Blood and lymphatic system disorders Pancytopenia	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Vascular disorders Hypotension	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.79% 3/379 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Vascular disorders Embolism	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.79% 3/379 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Vascular disorders Haemorrhage	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.79% 3/379 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Vascular disorders Peripheral ischaemia	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Vascular disorders Embolism arterial	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Vascular disorders Hypertension	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Vascular disorders Iliac vein occlusion	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Vascular disorders Orthostatic hypotension	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Vascular disorders Peripheral embolism	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Vascular disorders Venous thrombosis limb	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Hepatobiliary disorders Cholangitis	1.1% 4/370 • Number of events 4 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	1.6% 6/379 • Number of events 6 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Hepatobiliary disorders Biliary obstruction	1.6% 6/370 • Number of events 6 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Hepatobiliary disorders Cholestasis	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Hepatobiliary disorders Hyperbilirubinaemia	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Hepatobiliary disorders Cholecystitis	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Hepatobiliary disorders Bile duct stenosis	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Hepatobiliary disorders Hepatitis	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Hepatobiliary disorders Hepatitis toxic	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Hepatobiliary disorders Hepatotoxicity	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Cerebrovascular accident	1.1% 4/370 • Number of events 4 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Ischaemic stroke	1.1% 4/370 • Number of events 4 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Cerebral haemorrhage	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Cerebral ischaemia	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Aphasia	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Cerebral infarction	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Embolic stroke	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Epilepsy	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Generalised tonic-clonic seizure	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Hemiparesis	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Hypoaesthesia	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Metabolic encephalopathy	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Myoclonus	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Pineal gland cyst	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Sciatica	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Seizure	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Transient ischaemic attack	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Tremor	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Blood bilirubin increased	1.4% 5/370 • Number of events 5 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.79% 3/379 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Neutrophil count decreased	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations SARS-CoV-2 test positive	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Gamma-glutamyltransferase increased	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations White blood cell count decreased	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Blood alkaline phosphatase increased	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Blood glucose abnormal	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations General physical condition abnormal	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Haemoglobin decreased	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Platelet count decreased	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Renal and urinary disorders Acute kidney injury	0.81% 3/370 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	2.4% 9/379 • Number of events 10 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Renal and urinary disorders Haematuria	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.79% 3/379 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Renal and urinary disorders Renal impairment	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Renal and urinary disorders Nephrolithiasis	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Renal and urinary disorders Renal failure	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Renal and urinary disorders Urinary retention	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Cardiac disorders Atrial fibrillation	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.79% 3/379 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Cardiac disorders Cardiac arrest	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Cardiac disorders Cardiac failure	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Cardiac disorders Acute myocardial infarction	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Cardiac disorders Angina pectoris	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Cardiac disorders Arrhythmia	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Cardiac disorders Atrial flutter	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Cardiac disorders Cardiac failure chronic	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Cardiac disorders Cardiac flutter	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Cardiac disorders Myocardial infarction	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Cardiac disorders Sinus node dysfunction	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Cardiac disorders Tachycardia	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Injury, poisoning and procedural complications Exposure to SARS-CoV-2	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	1.1% 4/379 • Number of events 4 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Injury, poisoning and procedural complications Hip fracture	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Injury, poisoning and procedural complications Fall	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Injury, poisoning and procedural complications Head injury	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Injury, poisoning and procedural complications Wound	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Psychiatric disorders Confusional state	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Psychiatric disorders Mental status changes	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Psychiatric disorders Anxiety	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Psychiatric disorders Delirium	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Psychiatric disorders Depression	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Psychiatric disorders Psychotic disorder	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Musculoskeletal and connective tissue disorders Back pain	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Musculoskeletal and connective tissue disorders Chest wall haematoma	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Musculoskeletal and connective tissue disorders Pain in extremity	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Peritumoural oedema	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Skin and subcutaneous tissue disorders Rash	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Ear and labyrinth disorders Vertigo	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Reproductive system and breast disorders Penile vein thrombosis	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Reproductive system and breast disorders Priapism	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Eye disorders Retinal vein occlusion	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Product Issues Thrombosis in device	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Diarrhoea	6.2% 23/370 • Number of events 28 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	2.4% 9/379 • Number of events 9 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Vomiting	5.9% 22/370 • Number of events 26 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	1.6% 6/379 • Number of events 6 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Nausea	4.9% 18/370 • Number of events 24 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.79% 3/379 • Number of events 4 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Abdominal pain	2.4% 9/370 • Number of events 10 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	2.1% 8/379 • Number of events 8 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations COVID-19	4.9% 18/370 • Number of events 18 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	3.7% 14/379 • Number of events 14 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Pneumonia	1.9% 7/370 • Number of events 7 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	3.4% 13/379 • Number of events 13 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Pyrexia	2.2% 8/370 • Number of events 9 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	3.2% 12/379 • Number of events 14 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.7% 10/370 • Number of events 10 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	1.8% 7/379 • Number of events 7 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Blood and lymphatic system disorders Anaemia	1.4% 5/370 • Number of events 6 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	2.1% 8/379 • Number of events 8 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Vascular disorders Deep vein thrombosis	1.1% 4/370 • Number of events 4 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	2.1% 8/379 • Number of events 8 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Ascites	1.6% 6/370 • Number of events 7 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	1.3% 5/379 • Number of events 6 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Colitis	1.9% 7/370 • Number of events 7 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	1.1% 4/379 • Number of events 4 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Constipation	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	1.6% 6/379 • Number of events 6 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.81% 3/370 • Number of events 5 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	1.1% 4/379 • Number of events 4 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Intestinal obstruction	0.81% 3/370 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Ileus	0.81% 3/370 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.79% 3/379 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Duodenal obstruction	0.54% 2/370 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Duodenal stenosis	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Duodenal ulcer	0.81% 3/370 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Small intestinal obstruction	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Gastric haemorrhage	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Gastrointestinal toxicity	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Haematemesis	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Obstruction gastric	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Oesophagitis	0.54% 2/370 • Number of events 2 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.53% 2/379 • Number of events 4 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Abdominal pain upper	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Diarrhoea haemorrhagic	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Duodenal ulcer perforation	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Dysphagia	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Enterocolitis	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Faecaloma	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Food poisoning	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Gastric fistula	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Intestinal pseudo-obstruction	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Mesenteric vein thrombosis	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Neutropenic colitis	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Odynophagia	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Oesophageal ulcer	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Oesophageal varices haemorrhage	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Small intestinal haemorrhage	0.00% 0/370 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.26% 1/379 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Terminal ileitis	0.27% 1/370 • Number of events 1 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	0.00% 0/379 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Sepsis	1.6% 6/370 • Number of events 6 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	4.2% 16/379 • Number of events 18 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.

Other adverse events

Measure	NALIRIFOX n=370 participants at risk Participants were treated with irinotecan liposome injection 50 mg/m\^2 followed by oxaliplatin 60 mg/m\^2, followed by LV 400 mg/m\^2 and then 5-FU 2400 mg/m\^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.	Nab-paclitaxel+Gemcitabine n=379 participants at risk Participants were treated with nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 IV on Days 1, 8 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
Gastrointestinal disorders Diarrhoea	69.7% 258/370 • Number of events 566 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	35.6% 135/379 • Number of events 221 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Nausea	58.1% 215/370 • Number of events 406 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	42.7% 162/379 • Number of events 216 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Vomiting	37.6% 139/370 • Number of events 222 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	25.3% 96/379 • Number of events 168 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Stomatitis	13.5% 50/370 • Number of events 81 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	11.9% 45/379 • Number of events 54 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Constipation	25.1% 93/370 • Number of events 115 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	29.8% 113/379 • Number of events 141 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Abdominal pain	24.9% 92/370 • Number of events 110 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	19.8% 75/379 • Number of events 80 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Dry mouth	7.6% 28/370 • Number of events 29 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	3.7% 14/379 • Number of events 16 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Fatigue	32.4% 120/370 • Number of events 173 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	37.7% 143/379 • Number of events 183 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Asthenia	29.7% 110/370 • Number of events 164 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	26.6% 101/379 • Number of events 166 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Oedema peripheral	14.1% 52/370 • Number of events 60 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	28.2% 107/379 • Number of events 134 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Mucosal inflammation	13.5% 50/370 • Number of events 60 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	4.2% 16/379 • Number of events 20 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Pyrexia	8.9% 33/370 • Number of events 43 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	22.2% 84/379 • Number of events 129 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Neuropathy peripheral	17.8% 66/370 • Number of events 89 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	17.4% 66/379 • Number of events 92 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Dysgeusia	17.0% 63/370 • Number of events 74 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	15.3% 58/379 • Number of events 67 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Peripheral sensory neuropathy	15.1% 56/370 • Number of events 79 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	13.5% 51/379 • Number of events 60 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Paraesthesia	11.9% 44/370 • Number of events 53 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	8.7% 33/379 • Number of events 41 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Blood and lymphatic system disorders Neutropenia	29.2% 108/370 • Number of events 264 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	31.9% 121/379 • Number of events 278 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Blood and lymphatic system disorders Anaemia	25.4% 94/370 • Number of events 134 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	39.8% 151/379 • Number of events 196 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Blood and lymphatic system disorders Thrombocytopenia	13.5% 50/370 • Number of events 93 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	22.2% 84/379 • Number of events 173 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Blood and lymphatic system disorders Leukopenia	4.9% 18/370 • Number of events 40 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	6.3% 24/379 • Number of events 43 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Neutrophil count decreased	19.7% 73/370 • Number of events 208 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	18.2% 69/379 • Number of events 126 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Platelet count decreased	10.5% 39/370 • Number of events 71 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	17.7% 67/379 • Number of events 109 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Weight decreased	22.2% 82/370 • Number of events 92 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	8.7% 33/379 • Number of events 34 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Alanine aminotransferase increased	12.2% 45/370 • Number of events 64 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	12.7% 48/379 • Number of events 64 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Aspartate aminotransferase increased	10.8% 40/370 • Number of events 58 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	10.6% 40/379 • Number of events 55 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations White blood cell count decreased	4.3% 16/370 • Number of events 24 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	8.4% 32/379 • Number of events 54 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Decreased appetite	35.7% 132/370 • Number of events 157 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	17.9% 68/379 • Number of events 136 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Hypokalaemia	31.4% 116/370 • Number of events 190 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	12.9% 49/379 • Number of events 70 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Dehydration	9.5% 35/370 • Number of events 40 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	7.7% 29/379 • Number of events 31 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Skin and subcutaneous tissue disorders Alopecia	14.1% 52/370 • Number of events 53 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	31.4% 119/379 • Number of events 120 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Skin and subcutaneous tissue disorders Rash	3.0% 11/370 • Number of events 12 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	9.0% 34/379 • Number of events 37 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.81% 3/370 • Number of events 3 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	6.6% 25/379 • Number of events 30 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.8% 14/370 • Number of events 15 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	11.3% 43/379 • Number of events 49 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Musculoskeletal and connective tissue disorders Myalgia	3.5% 13/370 • Number of events 15 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	8.2% 31/379 • Number of events 43 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Abdominal pain upper	7.3% 27/370 • Number of events 34 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	5.5% 21/379 • Number of events 29 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Flatulence	8.1% 30/370 • Number of events 33 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	4.7% 18/379 • Number of events 21 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Dyspepsia	6.2% 23/370 • Number of events 32 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	4.7% 18/379 • Number of events 20 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Abdominal distension	5.9% 22/370 • Number of events 26 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	3.4% 13/379 • Number of events 15 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Gastrointestinal disorders Haemorrhoids	5.1% 19/370 • Number of events 22 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	3.2% 12/379 • Number of events 13 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
General disorders Chills	1.6% 6/370 • Number of events 6 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	5.0% 19/379 • Number of events 20 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Dizziness	6.5% 24/370 • Number of events 25 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	10.6% 40/379 • Number of events 44 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Headache	6.2% 23/370 • Number of events 37 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	5.0% 19/379 • Number of events 24 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Polyneuropathy	4.3% 16/370 • Number of events 19 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	5.0% 19/379 • Number of events 20 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Nervous system disorders Neurotoxicity	5.7% 21/370 • Number of events 35 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	3.4% 13/379 • Number of events 22 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Hypoalbuminaemia	7.0% 26/370 • Number of events 33 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	7.9% 30/379 • Number of events 31 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Hypomagnesaemia	9.2% 34/370 • Number of events 44 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	4.2% 16/379 • Number of events 22 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Metabolism and nutrition disorders Hyponatraemia	4.9% 18/370 • Number of events 21 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	5.3% 20/379 • Number of events 21 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Gamma-glutamyltransferase increased	11.9% 44/370 • Number of events 54 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	9.0% 34/379 • Number of events 35 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Blood alkaline phosphatase increased	10.5% 39/370 • Number of events 42 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	8.2% 31/379 • Number of events 33 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Investigations Blood bilirubin increased	5.7% 21/370 • Number of events 23 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	5.8% 22/379 • Number of events 23 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Skin and subcutaneous tissue disorders Pruritus	3.2% 12/370 • Number of events 14 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	5.8% 22/379 • Number of events 26 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Infections and infestations Urinary tract infection	7.3% 27/370 • Number of events 29 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	6.1% 23/379 • Number of events 29 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.5% 24/370 • Number of events 28 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	11.9% 45/379 • Number of events 48 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	5.4% 20/370 • Number of events 20 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	6.3% 24/379 • Number of events 24 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Respiratory, thoracic and mediastinal disorders Cough	3.8% 14/370 • Number of events 18 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	7.9% 30/379 • Number of events 31 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Musculoskeletal and connective tissue disorders Back pain	7.6% 28/370 • Number of events 37 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	8.7% 33/379 • Number of events 36 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Musculoskeletal and connective tissue disorders Arthralgia	3.5% 13/370 • Number of events 16 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	7.9% 30/379 • Number of events 41 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Musculoskeletal and connective tissue disorders Muscular weakness	4.6% 17/370 • Number of events 22 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	5.5% 21/379 • Number of events 24 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Musculoskeletal and connective tissue disorders Pain in extremity	1.9% 7/370 • Number of events 8 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	7.9% 30/379 • Number of events 35 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Vascular disorders Hypotension	5.7% 21/370 • Number of events 27 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	6.6% 25/379 • Number of events 26 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Vascular disorders Hypertension	5.7% 21/370 • Number of events 24 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	4.0% 15/379 • Number of events 19 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Psychiatric disorders Insomnia	7.6% 28/370 • Number of events 28 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	8.4% 32/379 • Number of events 32 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
Psychiatric disorders Anxiety	2.7% 10/370 • Number of events 10 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.	6.3% 24/379 • Number of events 25 • Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days) The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.

Additional Information

Medical Director

Ipsen Pharma

Phone: see email

Email: clinical.trials@ipsen.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER