Trial Outcomes & Findings for A Study of Epacadostat (INCB024360) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced Solid Tumors (ECHO-203) (NCT NCT02318277)

Last Updated: 2022-01-13

Results Overview

Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

176 participants

Primary outcome timeframe

Duration of study treatment and up to 90 days after the last dose [approximately 3 years]

Results posted on

2022-01-13

Participant Flow

This study was conducted at 13 study sites in the United States. Participants were enrolled at 12 study sites.

A total of 235 participants were screened and 59 participants were screen failures. A total of 176 participants ( 34 participants in Phase 1 and 142 in Phase 2) were enrolled in the study. Study enrollment was permanently discontinued on 24 Apr 2018 as a strategic decision. At the time of data cut-off, 28 Aug 2019, 1 participant was ongoing.

Participant milestones

Participant milestones
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.
Overall Study COMPLETED	0	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	6	3	4	4	8	9	49	93
Overall Study STARTED	6	3	4	4	8	9	49	93

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.
Overall Study Physician Decision	0	0	0	0	0	0	0	1
Overall Study Other	0	0	0	0	0	0	1	0
Overall Study Withdrawal by Subject	0	0	1	0	1	1	6	14
Overall Study Participant trial terminated by sponsor	0	0	1	0	1	2	5	16
Overall Study Lost to Follow-up	1	0	1	0	0	0	3	4
Overall Study Death	5	3	1	4	6	5	34	58
Overall Study Transitioned to Hospice	0	0	0	0	0	1	0	0

Baseline Characteristics

A Study of Epacadostat (INCB024360) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced Solid Tumors (ECHO-203)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) n=6 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) n=3 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) n=4 Participants Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) n=4 Participants Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=8 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=9 Participants Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=49 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=93 Participants Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Total n=176 Participants Total of all reporting groups
Age, Continuous	70.8 Years STANDARD_DEVIATION 4.79 • n=5 Participants	75.7 Years STANDARD_DEVIATION 7.23 • n=7 Participants	65.3 Years STANDARD_DEVIATION 9.07 • n=5 Participants	72.3 Years STANDARD_DEVIATION 7.59 • n=4 Participants	58.6 Years STANDARD_DEVIATION 8.65 • n=21 Participants	63.4 Years STANDARD_DEVIATION 7.75 • n=10 Participants	60.2 Years STANDARD_DEVIATION 13.24 • n=115 Participants	64 Years STANDARD_DEVIATION 10.27 • n=24 Participants	63.3 Years STANDARD_DEVIATION 11.11 • n=42 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	5 Participants n=10 Participants	19 Participants n=115 Participants	25 Participants n=24 Participants	57 Participants n=42 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	7 Participants n=21 Participants	4 Participants n=10 Participants	30 Participants n=115 Participants	68 Participants n=24 Participants	119 Participants n=42 Participants
Race/Ethnicity, Customized White	6 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	7 Participants n=21 Participants	9 Participants n=10 Participants	41 Participants n=115 Participants	83 Participants n=24 Participants	157 Participants n=42 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	5 Participants n=115 Participants	5 Participants n=24 Participants	11 Participants n=42 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	3 Participants n=24 Participants	4 Participants n=42 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	2 Participants n=24 Participants	3 Participants n=42 Participants
Race/Ethnicity, Customized Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	0 Participants n=24 Participants	1 Participants n=42 Participants
Race/Ethnicity, Customized Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	3 Participants n=24 Participants	7 Participants n=42 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	8 Participants n=21 Participants	9 Participants n=10 Participants	46 Participants n=115 Participants	87 Participants n=24 Participants	164 Participants n=42 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=24 Participants	1 Participants n=42 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants	2 Participants n=24 Participants	4 Participants n=42 Participants

PRIMARY outcome

Timeframe: Duration of study treatment and up to 90 days after the last dose [approximately 3 years]

Population: The Phase 1 safety population includes all subjects enrolled in the Phase 1 portion of the study who received at least 1 dose of INCB024360 or MEDI4736. Treatment groups were determined according to the actual treatment the subject received on Day 1 regardless of the actual study drug the subject received during participation in the study.

Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment

Outcome measures

Outcome measures
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) n=6 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) n=3 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) n=4 Participants Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) n=4 Participants Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=8 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=9 Participants Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.
Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE)	6 Participants	3 Participants	4 Participants	4 Participants	8 Participants	9 Participants	—	—

PRIMARY outcome

Timeframe: Measured every 8 weeks for duration of study treatment [approximately 12 months]

Population: Intent-to-Treat Population : All subjects who are enrolled in the Phase 2 portion of the study.

ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Outcome measures

Outcome measures
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) n=49 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) n=93 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.
Phase 2: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	6 Participants	12 Participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Measured every 8 weeks for duration of study treatment [approximately 6 months]

Population: Intent-to-Treat Population: All subjects who are enrolled in the Phase 1 portion of the study. Treatment groups for this population were defined according to the treatment assignment at the time of enrollment on Day 1 regardless of the actual study drug the subject received during his/her continued participation in the study.

Outcome measures

Outcome measures
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) n=6 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) n=3 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) n=4 Participants Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) n=4 Participants Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=8 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=9 Participants Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.
Phase 1: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified RECIST v1.1	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: Continuously for duration of study treatment and up to 90 days after the last dose [approximately 3 years]

Population: The Phase 2 safety population includes all subjects enrolled in the Phase 2 portion of the study who received at least 1 dose of INCB024360 or MEDI4736.

Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment

Outcome measures

Outcome measures
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) n=49 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) n=93 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.
Phase 2: Number of Treatment-Emergent Adverse Events	49 Participants	93 Participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Measured every 8 weeks for duration of active study treatment [approximately 24 months]

Population: Intent-to-Treat Population: All subjects who are enrolled in the Phase 1 \& 2 portion of the study. Treatment groups were defined at the time of enrollment on Day 1 according to the treatment assignment for Phase 1 and according to the tumor type for phase 2.

Defined as the time from earliest date of disease response until the earliest date of disease progression per RECIST v1.1, or death due to any cause, if occurring sooner than progression.

Outcome measures

Outcome measures
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) n=1 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) n=1 Participants Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=1 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=2 Participants Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=6 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=12 Participants Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.
Phase 1 and 2: Durability of Response as Measured by the Time From the Earliest Date of Disease Response Until Earliest Date of Disease Progression	1.9 months Upper and Lower bound not estimable due to sample size	—	NA months Median not estimable due to censoring	—	NA months Median not estimable due to censoring	NA months Interval 25.6 to Median not estimable due to censoring	13.8 months Interval 8.5 to Due to the definition of confidence interval in SAS proc lifetest, the time point satisfying the upper bound from the formula happens to be censored, therefore it is not NE	NA months Interval 1.9 to Median duration and Upper bound is not estimable due to due to the many censored observations

SECONDARY outcome

Timeframe: Measured every 8 weeks for duration of active study treatment [approximately 24 months]

Outcome measures

Outcome measures
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) n=6 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) n=3 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) n=4 Participants Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) n=4 Participants Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=8 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=9 Participants Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=49 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=93 Participants Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.
Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death	2.4 Months Interval 1.3 to 7.3	12.0 Months Interval 1.8 to Due to the definition of confidence interval in SAS proc lifetest, the time point satisfying the upper bound from the formula happens to be censored, therefore it is not estimable	1.9 Months Interval 1.1 to Due to the definition of confidence interval in SAS proc lifetest, the time point satisfying the upper bound from the formula happens to be censored, therefore it is not estimable	1.7 Months Interval 0.5 to 5.9	4.1 Months Interval 0.7 to Due to the definition of confidence interval in SAS proc lifetest, the time point satisfying the upper bound from the formula happens to be censored, therefore it is not estimable	2.5 Months Interval 1.1 to 27.2	1.9 Months Interval 1.7 to 2.3	2.1 Months Interval 1.9 to 3.7

SECONDARY outcome

Timeframe: Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1

Population: The PK evaluable population will include all subjects who received at least 1 dose of INCB024360 and provided at least 1 post dose plasma sample (1 PK/PD measurement). Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg)" Arm/Group were combined with the data collected from participants in the "Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg)" Arm/Group for PK Analysis.

Outcome measures

Outcome measures
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) n=8 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) n=3 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) n=3 Participants Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) n=7 Participants Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=7 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=38 Participants Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=36 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.
Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Peak Concentration	273 nM Standard Deviation 65.3	248 nM Standard Deviation 135	604 nM Standard Deviation 493	727 nM Standard Deviation 403	2660 nM Standard Deviation 1200	960 nM Standard Deviation 499	2500 nM Standard Deviation 1190	—

SECONDARY outcome

Timeframe: Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1

Outcome measures

Outcome measures
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) n=8 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) n=3 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) n=3 Participants Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) n=7 Participants Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=7 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=38 Participants Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=36 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.
Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Time to Maximal Observed Concentration	2.0 hours Interval 1.0 to 2.2	2.0 hours Interval 1.0 to 3.8	1.9 hours Interval 0.017 to 3.9	2.0 hours Interval 0.92 to 6.0	3.3 hours Interval 1.2 to 6.0	2.0 hours Interval 0.0 to 5.7	2.1 hours Interval 0.52 to 5.5	—

SECONDARY outcome

Timeframe: Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1

Outcome measures

Outcome measures
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) n=8 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) n=3 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) n=3 Participants Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) n=7 Participants Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=7 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=36 Participants Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=34 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.
Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Area Under the Concentration-time Curve	1040 h*nM Standard Deviation 345	1580 h*nM Standard Deviation 739	3090 h*nM Standard Deviation 1880	3650 h*nM Standard Deviation 2710	15400 h*nM Standard Deviation 6770	4130 h*nM Standard Deviation 1960	12200 h*nM Standard Deviation 5950	—

SECONDARY outcome

Timeframe: Measured at defined study visits from Cycle 1 Day 1 through cycle 2 [approximately 2 weeks].

Population: Evaluable Patients Post-Baseline: Treatment-Induced ADA - Patients who had baseline negative ADA result who developed anti-drug antibodies at any time after initial drug administration.

Outcome measures

Outcome measures
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) n=4 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) n=2 Participants Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) n=3 Participants Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) n=3 Participants Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=7 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=8 Participants Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=36 Participants Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.
Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants

Adverse Events

Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg)

Serious events: 2 serious events

Other events: 6 other events

Deaths: 5 deaths

Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 3 deaths

Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg)

Serious events: 2 serious events

Other events: 4 other events

Deaths: 1 deaths

Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 4 deaths

Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg)

Serious events: 4 serious events

Other events: 8 other events

Deaths: 6 deaths

Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg)

Serious events: 3 serious events

Other events: 9 other events

Deaths: 5 deaths

Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg)

Serious events: 20 serious events

Other events: 48 other events

Deaths: 35 deaths

Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg)

Serious events: 54 serious events

Other events: 87 other events

Deaths: 58 deaths

Serious adverse events

Serious adverse events
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) n=6 participants at risk Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) n=3 participants at risk Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) n=4 participants at risk Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) n=4 participants at risk Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=8 participants at risk Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=9 participants at risk Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=49 participants at risk Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=93 participants at risk Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 2/8 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Psychiatric disorders Agitation	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Alanine aminotransferase increased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Amylase increased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Blood and lymphatic system disorders Anaemia	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Immune system disorders Anaphylactic reaction	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Vascular disorders Angiopathy	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Ascites	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Aspartate aminotransferase increased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Asthenia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	3.2% 3/93 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Cardiac disorders Atrial fibrillation	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Bacteraemia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Hepatobiliary disorders Bile duct stenosis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Blood alkaline phosphatase increased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Blood calcium increased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Blood creatinine increased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Cardiac disorders Cardiac failure congestive	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Cellulitis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Cerebrovascular accident	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Chest pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Colitis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Psychiatric disorders Confusional state	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Constipation	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Injury, poisoning and procedural complications Contrast media reaction	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Convulsion	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Decreased appetite	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Vascular disorders Deep vein thrombosis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Dehydration	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Psychiatric disorders Delirium	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Depressed level of consciousness	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Device related sepsis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Diarrhoea	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Disease progression	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Dizziness	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Dysphagia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	3.2% 3/93 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.2% 5/49 • Number of events 7 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Vascular disorders Embolism	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Face oedema	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Injury, poisoning and procedural complications Fall	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Fatigue	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Gastric haemorrhage	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Renal and urinary disorders Haematuria	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Hepatobiliary disorders Hepatic failure	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Vascular disorders Hypertensive emergency	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Hypoaesthesia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Vascular disorders Hypotension	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Intestinal perforation	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Laryngeal haemorrhage	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Blood and lymphatic system disorders Leukocytosis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Lipase increased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Localised oedema	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Lung infection	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Multi-organ failure	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Nausea	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Non-cardiac chest pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Oedema peripheral	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Cardiac disorders Pericardial effusion	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Pharyngeal haemorrhage	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Pleural effusion	16.7% 1/6 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Pneumonia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Polyneuropathy	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Presyncope	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Cardiac disorders Pulseless electrical activity	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Pyrexia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	3.2% 3/93 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Renal and urinary disorders Renal failure acute	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Sepsis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Cardiac disorders Sinus tachycardia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Skin infection	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Soft tissue infection	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of head and neck	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Stridor	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Cardiac disorders Supraventricular tachycardia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Syncope	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Cardiac disorders Tachycardia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Transient ischaemic attack	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Urinary tract infection	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	3.2% 3/93 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Renal and urinary disorders Urinary tract obstruction	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Urosepsis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Eye disorders Vision blurred	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Vomiting	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.2% 4/49 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	3.2% 3/93 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Injury, poisoning and procedural complications Wound	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]

Other adverse events

Other adverse events
Measure	Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) n=6 participants at risk Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) n=3 participants at risk Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) n=4 participants at risk Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) n=4 participants at risk Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=8 participants at risk Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=9 participants at risk Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle.	Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) n=49 participants at risk Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.	Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) n=93 participants at risk Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types.
Endocrine disorders Hyperthyroidism	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Abdominal distension	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 2/8 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	22.2% 2/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.2% 5/49 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.8% 10/93 • Number of events 10 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Abdominal pain lower	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Abdominal pain upper	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	37.5% 3/8 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Alanine aminotransferase increased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 3/9 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.8% 10/93 • Number of events 13 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Amylase increased	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.5% 6/93 • Number of events 11 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Blood and lymphatic system disorders Anaemia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 3/9 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	22.4% 11/49 • Number of events 11 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.8% 11/93 • Number of events 13 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Cardiac disorders Angina pectoris	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Psychiatric disorders Anxiety	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.2% 4/49 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.5% 6/93 • Number of events 7 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	22.2% 2/9 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.2% 6/49 • Number of events 7 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	9.7% 9/93 • Number of events 15 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Aspartate aminotransferase increased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 3/9 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.2% 5/49 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.8% 11/93 • Number of events 13 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Asthenia	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 2/8 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	14.3% 7/49 • Number of events 7 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.8% 10/93 • Number of events 10 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Blood albumin decreased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	3.2% 3/93 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Blood alkaline phosphatase increased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	22.2% 2/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.9% 12/93 • Number of events 13 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Blood bilirubin increased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Blood creatinine increased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	22.2% 2/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.2% 4/49 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	16.1% 15/93 • Number of events 18 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Blood potassium decreased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Blood prolactin abnormal	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Blood testosterone decreased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Reproductive system and breast disorders Breast mass	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Bronchitis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Candida infection	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Eye disorders Cataract	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Catheter site discharge	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Chills	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.2% 6/49 • Number of events 7 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.6% 8/93 • Number of events 10 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Clostridium difficile colitis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Psychiatric disorders Confusional state	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Eye disorders Conjunctivitis allergic	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Constipation	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	50.0% 2/4 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 2/8 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	22.4% 11/49 • Number of events 11 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	21.5% 20/93 • Number of events 21 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Cough	33.3% 2/6 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	66.7% 2/3 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	50.0% 2/4 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	22.2% 2/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	14.3% 7/49 • Number of events 9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	20.4% 19/93 • Number of events 26 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Decreased appetite	33.3% 2/6 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	22.2% 2/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	18.4% 9/49 • Number of events 12 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	28.0% 26/93 • Number of events 26 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Dehydration	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.2% 5/49 • Number of events 6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	15.1% 14/93 • Number of events 17 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Dental caries	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Psychiatric disorders Depression	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Diarrhoea	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 2/8 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 3/9 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	20.4% 10/49 • Number of events 15 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	23.7% 22/93 • Number of events 28 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Dizziness	16.7% 1/6 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.2% 5/49 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	9.7% 9/93 • Number of events 10 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Eye disorders Dry eye	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Dry mouth	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	22.2% 2/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Dysgeusia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Dysphagia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	22.2% 2/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.7% 1/6 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.2% 5/49 • Number of events 7 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	14.0% 13/93 • Number of events 18 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Ejection fraction decreased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Epigastric discomfort	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Skin and subcutaneous tissue disorders Erythema	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Eye infection	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Face oedema	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Injury, poisoning and procedural complications Fall	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.2% 4/49 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	7.5% 7/93 • Number of events 9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Fatigue	66.7% 4/6 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	50.0% 2/4 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	50.0% 2/4 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	37.5% 3/8 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	22.2% 2/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	51.0% 25/49 • Number of events 28 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	53.8% 50/93 • Number of events 54 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Flatulence	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Injury, poisoning and procedural complications Foreign body aspiration	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Gastric ulcer	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Gastritis	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Renal and urinary disorders Haematuria	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Haemorrhoidal haemorrhage	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Headache	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	50.0% 2/4 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.2% 6/49 • Number of events 8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	17.2% 16/93 • Number of events 20 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Renal and urinary disorders Hydronephrosis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	7.5% 7/93 • Number of events 7 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.2% 5/49 • Number of events 12 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.6% 8/93 • Number of events 23 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Vascular disorders Hypertension	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.5% 6/93 • Number of events 8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Hypoalbuminaemia	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 2/8 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.2% 4/49 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.5% 6/93 • Number of events 6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Endocrine disorders Hypogonadism	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.6% 8/93 • Number of events 8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 7 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.2% 4/49 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.6% 8/93 • Number of events 10 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Vascular disorders Hypotension	33.3% 2/6 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Endocrine disorders Hypothyroidism	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	7.5% 7/93 • Number of events 7 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Hypoxia	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Impaired gastric emptying	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Influenza like illness	33.3% 2/6 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Psychiatric disorders Insomnia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.2% 5/49 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	17.2% 16/93 • Number of events 16 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations International normalised ratio increased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Injury, poisoning and procedural complications Laceration	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Blood and lymphatic system disorders Leukocytosis	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Blood and lymphatic system disorders Leukopenia	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Lipase increased	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.2% 5/49 • Number of events 8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	9.7% 9/93 • Number of events 10 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Renal and urinary disorders Lower urinary tract symptoms	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Lymphocyte count decreased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Melaena	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.2% 4/49 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 7 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.2% 4/49 • Number of events 6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	15.1% 14/93 • Number of events 16 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Nasopharyngitis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Nausea	66.7% 4/6 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	50.0% 4/8 • Number of events 6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 3/9 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	26.5% 13/49 • Number of events 19 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	30.1% 28/93 • Number of events 33 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	14.3% 7/49 • Number of events 7 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Neuropathy peripheral	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Blood and lymphatic system disorders Neutropenia	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Non-cardiac chest pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Oedema peripheral	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	37.5% 3/8 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.2% 5/49 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	9.7% 9/93 • Number of events 10 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Oral candidiasis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.6% 8/93 • Number of events 8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Cardiac disorders Palpitations	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Paraesthesia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Peritumoural oedema	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 2/8 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Pneumonia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Skin and subcutaneous tissue disorders Pruritus	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 2/8 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 3/9 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.2% 4/49 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	14.0% 13/93 • Number of events 17 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
General disorders Pyrexia	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	50.0% 2/4 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	37.5% 3/8 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	22.4% 11/49 • Number of events 12 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.8% 10/93 • Number of events 15 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Rales	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Skin and subcutaneous tissue disorders Rash	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.8% 10/93 • Number of events 11 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	18.4% 9/49 • Number of events 14 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.8% 10/93 • Number of events 13 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Rhonchi	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Serotonin syndrome	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Sinus headache	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Skin infection	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Somnolence	33.3% 2/6 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	1.1% 1/93 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Sputum discoloured	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Stomatitis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	8.6% 8/93 • Number of events 9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Skin and subcutaneous tissue disorders Swelling face	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Syncope	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Cardiac disorders Tachycardia	33.3% 2/6 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	3.2% 3/93 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Ear and labyrinth disorders Tinnitus	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Transaminases increased	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour flare	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	3.2% 3/93 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	22.2% 2/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	9.7% 9/93 • Number of events 9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Upper respiratory tract infection	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 1/3 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	3.2% 3/93 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Renal and urinary disorders Urinary retention	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Infections and infestations Urinary tract infection	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	10.2% 5/49 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	5.4% 5/93 • Number of events 6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Eye disorders Vision blurred	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.1% 3/49 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.3% 4/93 • Number of events 4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Nervous system disorders Vocal cord paralysis	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	12.5% 1/8 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/9 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/49 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/93 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Gastrointestinal disorders Vomiting	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 1/4 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	37.5% 3/8 • Number of events 3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	33.3% 3/9 • Number of events 5 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	14.3% 7/49 • Number of events 10 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	18.3% 17/93 • Number of events 20 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Investigations Weight decreased	16.7% 1/6 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	25.0% 2/8 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	22.2% 2/9 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.0% 1/49 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	6.5% 6/93 • Number of events 6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/6 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/3 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/4 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	0.00% 0/8 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	11.1% 1/9 • Number of events 1 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	4.1% 2/49 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]	2.2% 2/93 • Number of events 2 • Duration of study treatment and up to 90 days after the last dose [approximately 3 years]

Additional Information

Study Director

Incyte Corporation

Phone: 855-463-3463

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Clinical Study Agreement
Publication restrictions are in place

Restriction type: OTHER