Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET (NCT NCT03972488)

Last Updated: 2026-01-21

Results Overview

PFS is the time from randomization to the first line progression (centrally assessed according to RECIST 1.1) or death due to any cause. Progression is defined using Response Evaluation Criteria in Solid Tumor Criteria (RECIST 1.1) as a 20% increase in the sum of diameters of all measured target lesions or unequivocal progression of non-target lesions or appearance of a new lesion.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

226 participants

Primary outcome timeframe

from randomization to the first line progression or death due to any cause, up to approx. 42 months

Results posted on

2026-01-21

Participant Flow

This study randomized subjects in 38 centers in 9 participating countries. Overall, 222 subjects were planned to be randomized (2:1) to Lutathera arm or control arm.

Participant milestones

Participant milestones
Measure	Lutathera® Plus Octreotide LAR 30 mg (Investigational Arm) Lutathera treatment consisted of a cumulative administered radioactivity of 29.6 GBq (800mCi) (7.4 GBq/200 mCi x 4 administrations every 8 +/- 1 week). Participants in the Lutathera arm were concomitantly administered with octreotide LAR 30 mg (Sandostatin LAR Depot) the day after each administration of Lutathera and no earlier than 4 hours after completion of the Lutathera infusion. Once Lutathera treatment completed, participants continued the 4-week interval administrations of 30 mg octreotide LAR until the completion of the Treatment Phase. Concomitantly with Lutathera, sterile amino acid solution was administered to minimize renal radiation exposure during Lutathera treatment.	Octreotide LAR 60 mg (Control Arm) Participants were administered with octreotide LAR 60 mg (Sandostatin LAR Depot) at 4-week intervals until the completion of the Treatment Phase.
Overall Study STARTED	151	75
Overall Study Participants Treated in Treatment Period	147	73
Overall Study Participants Not Treated in Treatment Period	4	2
Overall Study Participants Entered Crossover Treatment Period	0	29
Overall Study Participants Entered Retreatment Period	8	0
Overall Study COMPLETED	78	15
Overall Study NOT COMPLETED	73	60

Reasons for withdrawal

Reasons for withdrawal
Measure	Lutathera® Plus Octreotide LAR 30 mg (Investigational Arm) Lutathera treatment consisted of a cumulative administered radioactivity of 29.6 GBq (800mCi) (7.4 GBq/200 mCi x 4 administrations every 8 +/- 1 week). Participants in the Lutathera arm were concomitantly administered with octreotide LAR 30 mg (Sandostatin LAR Depot) the day after each administration of Lutathera and no earlier than 4 hours after completion of the Lutathera infusion. Once Lutathera treatment completed, participants continued the 4-week interval administrations of 30 mg octreotide LAR until the completion of the Treatment Phase. Concomitantly with Lutathera, sterile amino acid solution was administered to minimize renal radiation exposure during Lutathera treatment.	Octreotide LAR 60 mg (Control Arm) Participants were administered with octreotide LAR 60 mg (Sandostatin LAR Depot) at 4-week intervals until the completion of the Treatment Phase.
Overall Study Progressive disease	42	44
Overall Study Physician Decision	13	7
Overall Study Adverse Event	8	1
Overall Study Death	4	4
Overall Study Withdrawal by Subject	3	4
Overall Study Other = untreated or stopped treatment by patient decision but agreed to be followed-up	3	0

Baseline Characteristics

Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lutathera® Plus Octreotide LAR 30 mg (Investigational Arm) n=151 Participants Lutathera treatment consisted of a cumulative administered radioactivity of 29.6 GBq (800mCi) (7.4 GBq/200 mCi x 4 administrations every 8 +/- 1 week). Participants in the Lutathera arm were concomitantly administered with octreotide LAR 30 mg (Sandostatin LAR Depot) the day after each administration of Lutathera and no earlier than 4 hours after completion of the Lutathera infusion. Once Lutathera treatment completed, participants continued the 4-week interval administrations of 30 mg octreotide LAR until the completion of the Treatment Phase. Concomitantly with Lutathera, sterile amino acid solution was administered to minimize renal radiation exposure during Lutathera treatment.	Octreotide LAR 60 mg (Control Arm) n=75 Participants Participants were administered with octreotide LAR 60 mg (Sandostatin LAR Depot) at 4-week intervals until the completion of the Treatment Phase.	Total n=226 Participants Total of all reporting groups
Age, Continuous	60.2 years STANDARD_DEVIATION 13.21 • n=37 Participants	59.6 years STANDARD_DEVIATION 11.52 • n=44 Participants	60.0 years STANDARD_DEVIATION 12.65 • n=40 Participants
Sex: Female, Male Female	70 Participants n=37 Participants	35 Participants n=44 Participants	105 Participants n=40 Participants
Sex: Female, Male Male	81 Participants n=37 Participants	40 Participants n=44 Participants	121 Participants n=40 Participants
Race/Ethnicity, Customized White	115 Participants n=37 Participants	50 Participants n=44 Participants	165 Participants n=40 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=37 Participants	2 Participants n=44 Participants	5 Participants n=40 Participants
Race/Ethnicity, Customized Asian (Indian & Korean)	23 Participants n=37 Participants	11 Participants n=44 Participants	34 Participants n=40 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=37 Participants	0 Participants n=44 Participants	1 Participants n=40 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=37 Participants	0 Participants n=44 Participants	1 Participants n=40 Participants
Race/Ethnicity, Customized Missing	8 Participants n=37 Participants	12 Participants n=44 Participants	20 Participants n=40 Participants

PRIMARY outcome

Timeframe: from randomization to the first line progression or death due to any cause, up to approx. 42 months

Population: Full Analysis Set (FAS) comprises all participants to whom study treatment has been assigned by randomization.

Outcome measures

Outcome measures
Measure	Lutathera® Plus Octreotide LAR 30 mg (Investigational Arm) n=151 Participants Lutathera treatment consisted of a cumulative administered radioactivity of 29.6 GBq (800mCi) (7.4 GBq/200 mCi x 4 administrations every 8 +/- 1 week). Participants in the Lutathera arm were concomitantly administered with octreotide LAR 30 mg (Sandostatin LAR Depot) the day after each administration of Lutathera and no earlier than 4 hours after completion of the Lutathera infusion. Once Lutathera treatment completed, participants continued the 4-week interval administrations of 30 mg octreotide LAR until the completion of the Treatment Phase. Concomitantly with Lutathera, sterile amino acid solution was administered to minimize renal radiation exposure during Lutathera treatment.	Octreotide LAR 60 mg (Control Arm) n=75 Participants Participants were administered with octreotide LAR 60 mg (Sandostatin LAR Depot) at 4-week intervals until the completion of the Treatment Phase.
Progression Free Survival (PFS) Per Central Assessment	22.8 months Interval 19.4 to NA: The upper limit of CI was not reached because of insufficient number of participants with events in the Lutathera arm	8.5 months Interval 7.7 to 13.8

SECONDARY outcome

Timeframe: Up to approx. 42 months

Population: FAS comprises all participants to whom study treatment has been assigned by randomization.

ORR is defined as the percentage of patients with the best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1. CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Outcome measures
Measure	Lutathera® Plus Octreotide LAR 30 mg (Investigational Arm) n=151 Participants Lutathera treatment consisted of a cumulative administered radioactivity of 29.6 GBq (800mCi) (7.4 GBq/200 mCi x 4 administrations every 8 +/- 1 week). Participants in the Lutathera arm were concomitantly administered with octreotide LAR 30 mg (Sandostatin LAR Depot) the day after each administration of Lutathera and no earlier than 4 hours after completion of the Lutathera infusion. Once Lutathera treatment completed, participants continued the 4-week interval administrations of 30 mg octreotide LAR until the completion of the Treatment Phase. Concomitantly with Lutathera, sterile amino acid solution was administered to minimize renal radiation exposure during Lutathera treatment.	Octreotide LAR 60 mg (Control Arm) n=75 Participants Participants were administered with octreotide LAR 60 mg (Sandostatin LAR Depot) at 4-week intervals until the completion of the Treatment Phase.
Overall Response Rate (ORR) Per Central Assessment (Key Secondary)	43.0 Percentage of participants Interval 35.0 to 51.3	9.3 Percentage of participants Interval 3.8 to 18.3

SECONDARY outcome

Timeframe: Up to approx. 42 months

Population: FAS comprises all participants to whom study treatment has been assigned by randomization.

TTD is defined as the first deterioration of at least 10 points from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30): global health status, diarrhea, fatigue, and pain. The Quality of Life Questionnaire C30 (QLQ-C30) was developed by the European Organization for Research and Treatment of Cancer (EORTC) to assess quality of life in cancer patients. It includes five function domains (physical, emotional, social, role, cognitive), eight symptoms (fatigue, pain, nausea/vomiting, constipation, diarrhea, insomnia, dyspnea, and appetite loss), as well as global health/quality-of-life and financial impact. Subjects respond on a four-point scale from "not at all" to "very much" for most items. Raw scores are linearly transformed so each score ranged a 0-100, where higher scores indicate worse symptoms (e.g., more severe/worsened) and lower scores indicate less symptoms (e.g., less severe/improvement).

Outcome measures

Outcome measures
Measure	Lutathera® Plus Octreotide LAR 30 mg (Investigational Arm) n=151 Participants Lutathera treatment consisted of a cumulative administered radioactivity of 29.6 GBq (800mCi) (7.4 GBq/200 mCi x 4 administrations every 8 +/- 1 week). Participants in the Lutathera arm were concomitantly administered with octreotide LAR 30 mg (Sandostatin LAR Depot) the day after each administration of Lutathera and no earlier than 4 hours after completion of the Lutathera infusion. Once Lutathera treatment completed, participants continued the 4-week interval administrations of 30 mg octreotide LAR until the completion of the Treatment Phase. Concomitantly with Lutathera, sterile amino acid solution was administered to minimize renal radiation exposure during Lutathera treatment.	Octreotide LAR 60 mg (Control Arm) n=75 Participants Participants were administered with octreotide LAR 60 mg (Sandostatin LAR Depot) at 4-week intervals until the completion of the Treatment Phase.
Time to Deteriration (TTD) Global Health Status, Diarrhea, Fatigue, Pain (EORTC QLQ-C30) (Key Secondary) Global Health status	13.2 months Interval 8.8 to 17.2	8.6 months Interval 5.8 to 14.0
Time to Deteriration (TTD) Global Health Status, Diarrhea, Fatigue, Pain (EORTC QLQ-C30) (Key Secondary) Fatigue	6.0 months Interval 3.4 to 6.8	6.0 months Interval 3.9 to 11.0
Time to Deteriration (TTD) Global Health Status, Diarrhea, Fatigue, Pain (EORTC QLQ-C30) (Key Secondary) Pain	10.3 months Interval 6.0 to 13.6	8.6 months Interval 3.9 to 13.7
Time to Deteriration (TTD) Global Health Status, Diarrhea, Fatigue, Pain (EORTC QLQ-C30) (Key Secondary) Diarrhea	17.4 months Interval 14.4 to 28.2	17.3 months Interval 8.1 to NA: The upper limit of CI was not reached because of insufficient number of participants with events in the Octreotide arm

SECONDARY outcome

Timeframe: Up to approx. 42 months

Population: FAS comprises all participants to whom study treatment has been assigned by randomization.

Disease Control Rate is the percentage of participants with a best overall response of complete response (CR), partial response (PR) or stable disease (SD) (centrally assessed according to RECIST 1.1). CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD).

Outcome measures

Outcome measures
Measure	Lutathera® Plus Octreotide LAR 30 mg (Investigational Arm) n=151 Participants Lutathera treatment consisted of a cumulative administered radioactivity of 29.6 GBq (800mCi) (7.4 GBq/200 mCi x 4 administrations every 8 +/- 1 week). Participants in the Lutathera arm were concomitantly administered with octreotide LAR 30 mg (Sandostatin LAR Depot) the day after each administration of Lutathera and no earlier than 4 hours after completion of the Lutathera infusion. Once Lutathera treatment completed, participants continued the 4-week interval administrations of 30 mg octreotide LAR until the completion of the Treatment Phase. Concomitantly with Lutathera, sterile amino acid solution was administered to minimize renal radiation exposure during Lutathera treatment.	Octreotide LAR 60 mg (Control Arm) n=75 Participants Participants were administered with octreotide LAR 60 mg (Sandostatin LAR Depot) at 4-week intervals until the completion of the Treatment Phase.
Disease Control Rate (DCR) Per Central Assessment	90.7 Percentage of participants Interval 84.9 to 94.8	66.7 Percentage of participants Interval 54.8 to 77.1

SECONDARY outcome

Timeframe: Up to approx. 42 months

Population: FAS comprises all participants to whom study treatment has been assigned by randomization. Only participants who had a response were analyzed.

Duration of Response defined as time from first complete or partial response to progression or death due to underlying cancer according to RECIST 1.1.

Outcome measures

Outcome measures
Measure	Lutathera® Plus Octreotide LAR 30 mg (Investigational Arm) n=65 Participants Lutathera treatment consisted of a cumulative administered radioactivity of 29.6 GBq (800mCi) (7.4 GBq/200 mCi x 4 administrations every 8 +/- 1 week). Participants in the Lutathera arm were concomitantly administered with octreotide LAR 30 mg (Sandostatin LAR Depot) the day after each administration of Lutathera and no earlier than 4 hours after completion of the Lutathera infusion. Once Lutathera treatment completed, participants continued the 4-week interval administrations of 30 mg octreotide LAR until the completion of the Treatment Phase. Concomitantly with Lutathera, sterile amino acid solution was administered to minimize renal radiation exposure during Lutathera treatment.	Octreotide LAR 60 mg (Control Arm) n=7 Participants Participants were administered with octreotide LAR 60 mg (Sandostatin LAR Depot) at 4-week intervals until the completion of the Treatment Phase.
Duration of Response (DOR) Per Central Assessment	23.3 months Interval 18.4 to NA: The upper limit of CI was not reached because of insufficient number of participants with events in the Lutathera arm	NA months NA: The median was not reached because of insufficient number of participants with events in the Octreotide arm

SECONDARY outcome

Timeframe: from FPFV until end of study (about 94 months)

Rate of adverse events scored according to CTCAE grade

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from FPFV until end of study (about 94 months)

Rate of laboratory toxicities scored according to CTCAE grade

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from FPFV until end of study (about 94 months)

OS is the time from randomization date until day of death due to any cause.

Outcome measures

Outcome data not reported

Adverse Events

Lutathera® Plus Octreotide LAR 30 mg

Serious events: 30 serious events

Other events: 129 other events

Deaths: 32 deaths

Octreotide LAR 60 mg (Control Arm)

Serious events: 15 serious events

Other events: 65 other events

Deaths: 14 deaths

Crossover Lutathera

Serious events: 2 serious events

Other events: 22 other events

Deaths: 3 deaths

Re-Treatment Lutathera

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Disclosure Office

Novartis Pharmaceuticals

Phone: 862-778-3000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e., data from all sites) in clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Lutathera® Plus Octreotide LAR 30 mg n=147 participants at risk Lutathera treatment consisted of a cumulative administered radioactivity of 29.6 GBq (800mCi) (7.4 GBq/200 mCi x 4 administrations every 8 +/- 1 week). Participants in the Lutathera arm were concomitantly administered with octreotide LAR 30 mg (Sandostatin LAR Depot) the day after each administration of Lutathera and no earlier than 4 hours after completion of the Lutathera infusion. Once Lutathera treatment completed, participants continued the 4-week interval administrations of 30 mg octreotide LAR until the completion of the Treatment Phase. Concomitantly with Lutathera, sterile amino acid solution was administered to minimize renal radiation exposure during Lutathera treatment.	Octreotide LAR 60 mg (Control Arm) n=73 participants at risk Participants were administered with octreotide LAR 60 mg (Sandostatin LAR Depot) at 4-week intervals until the completion of the Treatment Phase.	Crossover Lutathera n=29 participants at risk Participants who received Octreotide LAR in Active comparator Arm and who progressed and met cross over eligibility criteria received maximum 4 cycles of Lutathera (7.4 GBq/200 mCi x 4 cycles) plus octreotide long-acting (30 mg every 8 weeks)	Re-Treatment Lutathera n=8 participants at risk Participants who received Lutathera in experimental arm and who progressed and met re treatment eligibility criteria received additional 2-4 cycles of Lutathera (7.4 GBq/200 mCi x 4 cycles)
Blood and lymphatic system disorders Anaemia	1.4% 2/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Blood and lymphatic system disorders Lymphopenia	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Cardiac disorders Acute coronary syndrome	0.00% 0/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Cardiac disorders Angina unstable	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Cardiac disorders Bradycardia	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Cardiac disorders Carcinoid heart disease	0.00% 0/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Cardiac disorders Pulmonary valve disease	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Endocrine disorders Carcinoid syndrome	0.00% 0/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Abdominal pain	1.4% 2/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Ascites	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Diarrhoea	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Dysphagia	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Inguinal hernia	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Intestinal obstruction	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Intestinal perforation	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Nausea	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Rectal haemorrhage	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Small intestinal obstruction	3.4% 5/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Subileus	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Vomiting	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
General disorders Generalised oedema	0.00% 0/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
General disorders Infusion site extravasation	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
General disorders Oedema peripheral	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
General disorders Pyrexia	1.4% 2/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Hepatobiliary disorders Cholangitis	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	3.4% 1/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Hepatobiliary disorders Cholestasis	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Hepatobiliary disorders Gallbladder rupture	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Hepatobiliary disorders Hepatorenal syndrome	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Hepatobiliary disorders Jaundice	0.00% 0/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Infections and infestations Abdominal sepsis	0.00% 0/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Infections and infestations Appendicitis	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Infections and infestations COVID-19	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Infections and infestations Gastroenteritis	0.00% 0/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Infections and infestations Soft tissue infection	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Infections and infestations Urosepsis	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Injury, poisoning and procedural complications Fall	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Injury, poisoning and procedural complications Femoral neck fracture	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.

Other adverse events
Measure	Lutathera® Plus Octreotide LAR 30 mg n=147 participants at risk Lutathera treatment consisted of a cumulative administered radioactivity of 29.6 GBq (800mCi) (7.4 GBq/200 mCi x 4 administrations every 8 +/- 1 week). Participants in the Lutathera arm were concomitantly administered with octreotide LAR 30 mg (Sandostatin LAR Depot) the day after each administration of Lutathera and no earlier than 4 hours after completion of the Lutathera infusion. Once Lutathera treatment completed, participants continued the 4-week interval administrations of 30 mg octreotide LAR until the completion of the Treatment Phase. Concomitantly with Lutathera, sterile amino acid solution was administered to minimize renal radiation exposure during Lutathera treatment.	Octreotide LAR 60 mg (Control Arm) n=73 participants at risk Participants were administered with octreotide LAR 60 mg (Sandostatin LAR Depot) at 4-week intervals until the completion of the Treatment Phase.	Crossover Lutathera n=29 participants at risk Participants who received Octreotide LAR in Active comparator Arm and who progressed and met cross over eligibility criteria received maximum 4 cycles of Lutathera (7.4 GBq/200 mCi x 4 cycles) plus octreotide long-acting (30 mg every 8 weeks)	Re-Treatment Lutathera n=8 participants at risk Participants who received Lutathera in experimental arm and who progressed and met re treatment eligibility criteria received additional 2-4 cycles of Lutathera (7.4 GBq/200 mCi x 4 cycles)
Gastrointestinal disorders Abdominal discomfort	1.4% 2/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	2.7% 2/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	12.5% 1/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Blood and lymphatic system disorders Anaemia	18.4% 27/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	5.5% 4/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	6.9% 2/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Blood and lymphatic system disorders Lymphopenia	6.1% 9/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	3.4% 1/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Blood and lymphatic system disorders Neutropenia	2.7% 4/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	12.5% 1/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Blood and lymphatic system disorders Thrombocytopenia	8.2% 12/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	6.9% 2/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Abdominal distension	8.2% 12/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	8.2% 6/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	6.9% 2/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Abdominal pain	16.3% 24/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	27.4% 20/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	20.7% 6/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Abdominal pain upper	7.5% 11/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	8.2% 6/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	10.3% 3/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Constipation	10.2% 15/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	8.2% 6/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	3.4% 1/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Diarrhoea	25.9% 38/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	34.2% 25/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	13.8% 4/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Dyspepsia	4.8% 7/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	3.4% 1/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	12.5% 1/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Flatulence	7.5% 11/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	5.5% 4/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	3.4% 1/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Nausea	26.5% 39/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	17.8% 13/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	27.6% 8/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	37.5% 3/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Gastrointestinal disorders Vomiting	14.3% 21/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	8.2% 6/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	6.9% 2/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	12.5% 1/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
General disorders Asthenia	19.0% 28/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	12.3% 9/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	25.0% 2/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
General disorders Fatigue	19.7% 29/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	17.8% 13/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	24.1% 7/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
General disorders Injection site pain	2.7% 4/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	5.5% 4/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
General disorders Oedema peripheral	11.6% 17/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	6.8% 5/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	3.4% 1/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
General disorders Pain	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	3.4% 1/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	12.5% 1/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
General disorders Pyrexia	7.5% 11/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	4.1% 3/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Infections and infestations COVID-19	19.0% 28/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	13.7% 10/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	3.4% 1/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Investigations Alanine aminotransferase increased	10.9% 16/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	13.7% 10/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	13.8% 4/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Investigations Aspartate aminotransferase increased	10.9% 16/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	11.0% 8/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	13.8% 4/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Investigations Blood alkaline phosphatase increased	4.8% 7/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	5.5% 4/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	6.9% 2/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Investigations Blood bilirubin increased	2.7% 4/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	6.8% 5/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Investigations Blood creatinine increased	6.1% 9/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	2.7% 2/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Investigations Blood thyroid stimulating hormone increased	8.2% 12/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	5.5% 4/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	3.4% 1/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Investigations Creatinine renal clearance decreased	0.68% 1/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	12.5% 1/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Investigations Gamma-glutamyltransferase increased	8.2% 12/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	11.0% 8/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	6.9% 2/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Investigations Lymphocyte count decreased	10.9% 16/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	6.9% 2/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Investigations Neutrophil count decreased	6.1% 9/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Investigations Platelet count decreased	16.3% 24/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	5.5% 4/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	3.4% 1/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	12.5% 1/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Investigations Weight decreased	9.5% 14/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	2.7% 2/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	12.5% 1/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Investigations Weight increased	12.2% 18/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	6.8% 5/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	10.3% 3/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Investigations White blood cell count decreased	12.9% 19/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	4.1% 3/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	6.9% 2/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Metabolism and nutrition disorders Decreased appetite	12.9% 19/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	9.6% 7/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	10.3% 3/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	12.5% 1/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Metabolism and nutrition disorders Hyperglycaemia	13.6% 20/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	13.7% 10/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	6.9% 2/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Metabolism and nutrition disorders Hyperuricaemia	4.1% 6/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	1.4% 1/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	6.9% 2/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Metabolism and nutrition disorders Hypokalaemia	2.0% 3/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	5.5% 4/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.
Musculoskeletal and connective tissue disorders Arthralgia	9.5% 14/147 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	8.2% 6/73 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/29 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/8 • On-treatment AEs and deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, up to 42 months. Any sign or symptom that occurs during the conduct of the trial.