Trial Outcomes & Findings for A Study of R1507 in Participants With Recurrent or Refractory Sarcoma (NCT NCT00642941)

Last Updated: 2021-02-03

Results Overview

Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is \>=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

317 participants

Primary outcome timeframe

Baseline up to 6 years (assessed at baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression)

Results posted on

2021-02-03

Participant Flow

A screening period was included prior to administration of study drug. Tumor scans/X-rays were to be obtained within 4 weeks, fluro-D-glucose positron emission tomography (FDG-PET) scans within 2 weeks, and Baseline laboratory evaluations within 1 week before first dose.

Participant milestones

Participant milestones
Measure	Cohort 1: Ewings Sarcoma Primary Cohort Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 1 includes individuals with Ewing's sarcoma who have relapsed within 24 weeks after diagnosis and have received two or more prior chemotherapy regimens.	Cohort 2: Ewings Sarcoma Secondary Cohort Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors. Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
Overall Study STARTED	70	54	7	40	25	41	23	14	11	9	12	11
Overall Study COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	70	54	7	40	25	41	23	14	11	9	12	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: Ewings Sarcoma Primary Cohort Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 1 includes individuals with Ewing's sarcoma who have relapsed within 24 weeks after diagnosis and have received two or more prior chemotherapy regimens.	Cohort 2: Ewings Sarcoma Secondary Cohort Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors. Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
Overall Study Physician Decision	3	1	0	0	0	0	1	0	0	1	0	1
Overall Study Death	4	0	1	1	2	1	0	0	0	0	0	1
Overall Study Study closed by Sponsor	0	1	0	0	0	0	0	0	0	0	0	0
Overall Study Withdrawal by Subject	1	0	0	2	0	0	2	0	1	0	0	1
Overall Study Protocol Violation	0	0	0	0	0	0	1	0	0	0	0	0
Overall Study Adverse Event	1	1	0	0	0	0	1	1	0	1	0	0
Overall Study Other	1	1	1	1	0	1	0	1	0	0	0	1
Overall Study Disease progression	60	50	5	36	23	39	18	12	10	7	12	7

Baseline Characteristics

A Study of R1507 in Participants With Recurrent or Refractory Sarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Ewings Sarcoma Primary Cohort n=70 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 1 includes individuals with Ewing's sarcoma who have relapsed within 24 weeks after diagnosis and have received two or more prior chemotherapy regimens.	Cohort 2: Ewings Sarcoma Secondary Cohort n=54 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort n=7 Participants Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma n=40 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma n=25 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma n=41 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma n=23 Participants Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors. n=14 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma n=11 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma n=9 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma n=12 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified n=11 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.	Total n=317 Participants Total of all reporting groups
Age, Continuous	27 Years STANDARD_DEVIATION 10.72 • n=5 Participants	28.3 Years STANDARD_DEVIATION 12.9 • n=7 Participants	13.3 Years STANDARD_DEVIATION 3.15 • n=5 Participants	33.8 Years STANDARD_DEVIATION 18.83 • n=4 Participants	41.7 Years STANDARD_DEVIATION 16.11 • n=21 Participants	26.5 Years STANDARD_DEVIATION 12.21 • n=8 Participants	31.7 Years STANDARD_DEVIATION 13.67 • n=8 Participants	23.1 Years STANDARD_DEVIATION 6.09 • n=24 Participants	60.9 Years STANDARD_DEVIATION 11.27 • n=42 Participants	26.9 Years STANDARD_DEVIATION 11.01 • n=42 Participants	50.6 Years STANDARD_DEVIATION 11.06 • n=42 Participants	30.7 Years STANDARD_DEVIATION 18.56 • n=42 Participants	31.2 Years STANDARD_DEVIATION 13.36 • n=36 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	22 Participants n=7 Participants	3 Participants n=5 Participants	20 Participants n=4 Participants	11 Participants n=21 Participants	18 Participants n=8 Participants	12 Participants n=8 Participants	1 Participants n=24 Participants	3 Participants n=42 Participants	2 Participants n=42 Participants	3 Participants n=42 Participants	3 Participants n=42 Participants	118 Participants n=36 Participants
Sex: Female, Male Male	50 Participants n=5 Participants	32 Participants n=7 Participants	4 Participants n=5 Participants	20 Participants n=4 Participants	14 Participants n=21 Participants	23 Participants n=8 Participants	11 Participants n=8 Participants	13 Participants n=24 Participants	8 Participants n=42 Participants	7 Participants n=42 Participants	9 Participants n=42 Participants	8 Participants n=42 Participants	199 Participants n=36 Participants

PRIMARY outcome

Timeframe: Baseline up to 6 years (assessed at baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression)

Population: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment. There were 0 participants analyzed for Cohort 3 due to no efficacy data being collected for that cohort.

Outcome measures

Outcome measures
Measure	Cohort 2: Ewings Sarcoma Secondary Cohort n=54 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma n=40 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma n=25 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma n=41 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma n=23 Participants Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors. n=14 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma n=11 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma n=9 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma n=12 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified n=11 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.	Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8	11.11 Percentage of Participants	—	2.5 Percentage of Participants	4.0 Percentage of Participants	4.88 Percentage of Participants	0 Percentage of Participants	0 Percentage of Participants	0 Percentage of Participants	0 Percentage of Participants	0 Percentage of Participants	0 Percentage of Participants	—

PRIMARY outcome

Timeframe: Baseline up to 18 weeks (assessed at baseline, every 6 weeks until disease progression)

Population: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment.

The PFS survival rate is a landmark analysis of progression-free survival at 18 weeks from start of treatment. Progression-free survival rate at 18 weeks is a dichotomous endpoint, with a patient categorized as alive (with either stable disease or objective response) at 18 weeks from start of treatment.

Outcome measures

Outcome measures
Measure	Cohort 2: Ewings Sarcoma Secondary Cohort n=70 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors. Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.	Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
Progression-Free Survival (PFS) Rate According to WHO Response Criteria at 18 Weeks From Start of R2607 Treatment in Cohort 1	15.81 Percentage of Participants	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Baseline up to 6 years

Population: Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.

Outcome measures

Outcome measures
Measure	Cohort 2: Ewings Sarcoma Secondary Cohort n=70 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort n=54 Participants Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors. Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.	Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
Percentage of Participants With Adverse Events (AEs) in Cohort 1 and 2	96 percentage of participants	96 percentage of participants	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)

Population: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment.

Outcome measures

Outcome measures
Measure	Cohort 2: Ewings Sarcoma Secondary Cohort n=70 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors. Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.	Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
Percentage of Participants With Complete or Partial Response According to WHO Response Criteria in Cohort 1	8.57 percentage of participants	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, every 6 weeks until disease progression (up to 18 weeks)

Outcome measures

Outcome measures
Measure	Cohort 2: Ewings Sarcoma Secondary Cohort n=54 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma n=40 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma n=25 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma n=41 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma n=23 Participants Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors. n=14 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma n=11 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma n=9 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma n=12 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified n=11 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.	Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8	17.16 Percentage of Participants	—	19.69 Percentage of Participants	4.00 Percentage of Participants	7.32 Percentage of Participants	45.40 Percentage of Participants	8.16 Percentage of Participants	62.34 Percentage of Participants	0 Percentage of Participants	8.33 Percentage of Participants	22.86 Percentage of Participants	—

SECONDARY outcome

Timeframe: Baseline up to 6 years

Population: Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.

Outcome measures

Outcome measures
Measure	Cohort 2: Ewings Sarcoma Secondary Cohort n=7 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort n=40 Participants Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma n=25 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma n=41 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma n=23 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma n=14 Participants Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors. n=11 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma n=9 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma n=12 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma n=11 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.	Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
Percentage of Participants With AEs in Cohorts 3-8	85.7 percentage of participants	100 percentage of participants	100 percentage of participants	95 percentage of participants	91 percentage of participants	86 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)

Population: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment. There were 0 participants analyzed for Cohort 3, 7 and 8 due to no DOR data being collected for these cohorts.

The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is \>=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive.

Outcome measures

Outcome measures
Measure	Cohort 2: Ewings Sarcoma Secondary Cohort n=70 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort n=54 Participants Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma n=40 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma n=25 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma n=41 Participants Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors. Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.	Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
Duration of Response (DOR) According to WHO Response Criteria in Cohorts 1 to 8	44.29 weeks Interval 18.0 to Upper limit was not reached due to low number of events.	42.86 weeks Interval 18.14 to Upper limit was not reached due to low number of events.	—	NA weeks Interval 30.14 to DOR and upper limit were not reached due to low number of events.	13.14 weeks Interval 13.14 to Upper limit was not reached due to low number of events.	NA weeks Interval 21.0 to DOR and upper limit were not reached due to low number of events.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)

TTP is defined as the time from date of randomization until objective tumor progression. According to the WHO Response Criteria, objective tumor progression is \> 25% increase in the area of one or more measurable lesions or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Cohort 2: Ewings Sarcoma Secondary Cohort n=70 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort n=54 Participants Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma n=40 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma n=25 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma n=41 Participants Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors. n=23 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma n=14 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma n=11 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma n=9 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified n=12 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.	Cohort 8: Diagnosis Not Specified n=11 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8	6.00 weeks Interval 5.29 to 9.71	6.00 weeks Interval 5.71 to 8.14	—	5.71 weeks Interval 5.57 to 7.0	6.00 weeks Interval 5.57 to 6.43	5.50 weeks Interval 5.14 to 6.14	11.14 weeks Interval 6.0 to 17.71	6.14 weeks Interval 5.86 to 11.14	18.00 weeks Interval 5.71 to Upper limit was not reached due to low number of events.	5.57 weeks Interval 5.14 to 5.86	5.86 weeks Interval 5.29 to 8.43	6.14 weeks Interval 5.86 to 10.0

SECONDARY outcome

Timeframe: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)

Population: Data was not collected for this endpoint.

FFS was measured from the date of treatment start to the date of documented disease progression, relapse, or death from any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline until death (up to 6 years)

Population: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment. There were 0 participants analyzed for Cohort 3 and 7c due to no overall survival data being collected for those cohorts.

OS was measured from the time of study registration to the date of death or was censored at the date of last contact.

Outcome measures

Outcome measures
Measure	Cohort 2: Ewings Sarcoma Secondary Cohort n=70 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort n=54 Participants Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma n=40 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma n=25 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma n=61 Participants Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors. n=23 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma n=14 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma n=11 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma n=9 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified n=12 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.	Cohort 8: Diagnosis Not Specified n=11 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
Overall Survival (OS) in Cohorts 1 to 8	29.57 weeks Interval 20.57 to 37.57	43.57 weeks Interval 33.29 to 69.0	—	37.14 weeks Interval 25.57 to Upper limit was not reached due to low number of events.	40.71 weeks Interval 21.71 to 64.14	30.86 weeks Interval 21.57 to 50.0	42.43 weeks Interval 42.43 to Upper limit was not reached due to low number of events.	40.86 weeks Interval 23.57 to Upper limit was not reached due to low number of events.	NA weeks All participants were censored as no deaths occurred.	17.00 weeks Interval 9.14 to Upper limit was not reached due to low number of events.	36.00 weeks Interval 33.14 to Upper limit was not reached due to low number of events.	17.43 weeks Interval 13.0 to 30.14

SECONDARY outcome

Timeframe: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)

PFS is defined as the duration of time from start of treatment to time of objective progression or death.

Outcome measures

Outcome measures
Measure	Cohort 2: Ewings Sarcoma Secondary Cohort n=70 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort n=54 Participants Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma n=40 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma n=25 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma n=41 Participants Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors. n=23 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma n=14 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma n=11 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma n=9 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified n=12 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.	Cohort 8: Diagnosis Not Specified n=11 Participants Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
PFS According to WHO Response Criteria in Cohorts 1 to 8	6.00 weeks Interval 5.29 to 9.57	6.00 weeks Interval 5.71 to 8.14	—	5.71 weeks Interval 5.57 to 6.43	6.00 weeks Interval 5.43 to 6.14	5.43 weeks Interval 5.14 to 6.14	11.14 weeks Interval 5.71 to 11.71	6.14 weeks Interval 5.86 to 11.14	18.00 weeks Interval 5.71 to Upper limit was not reached due to low number of events.	5.57 weeks Interval 5.14 to 5.86	5.86 weeks Interval 5.29 to 8.43	6.14 weeks Interval 5.86 to 10.0

SECONDARY outcome

Timeframe: Predose (0 hours [h]), end of 60-90 minutes infusion (EOI), postdose (2, 24, 72-96 h) in Week 1; predose (0 h) and EOI in Weeks 2, 4, 6, 9; predose (0 h), EOI, postdose (48 h) in Week 12; predose (0 h) in Week 13, at final visit (up to 6 years)

Population: Data was not collected for this pharmacokinetic endpoint.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Predose (0 h), EOI (infusion over 60-90 minutes), postdose (2, 24, 72-96 h) in Week 1; predose (0 h) and EOI in Weeks 2, 4, 6, 9; predose (0 h), EOI, postdose (48 h) in Week 12; predose (0 h) in Week 13, at final visit (up to 6 years)

Population: Data was not collected for this pharmacokinetic endpoint.

Outcome measures

Outcome data not reported

Adverse Events

Cohort 1: Ewings Sarcoma Primary Cohort

Serious events: 11 serious events

Other events: 67 other events

Deaths: 9 deaths

Cohort 2: Ewings Sarcoma Secondary Cohort

Serious events: 13 serious events

Other events: 52 other events

Deaths: 5 deaths

Cohort 3: Ewings Sarcoma Expanded Cohort

Serious events: 1 serious events

Other events: 6 other events

Deaths: 2 deaths

Cohort 4: Osteosarcoma

Serious events: 4 serious events

Other events: 40 other events

Deaths: 7 deaths

Cohort 5: Synovial Sarcoma

Serious events: 5 serious events

Other events: 25 other events

Deaths: 3 deaths

Cohort 6: Rhabdomyosarcoma

Serious events: 4 serious events

Other events: 39 other events

Deaths: 3 deaths

Cohort 7a: Alveolar Soft Part Sarcoma

Serious events: 1 serious events

Other events: 21 other events

Deaths: 1 deaths

Cohort 7b: Desmoplastic Small Round Cell Tumors

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Cohort 7c: Extraskeletal Myxoid Chondrosarcoma

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Cohort 7d: Clear Cell Sarcoma

Serious events: 3 serious events

Other events: 9 other events

Deaths: 1 deaths

Cohort 7e: Myxoid Liposarcoma

Serious events: 2 serious events

Other events: 12 other events

Deaths: 1 deaths

Cohort 8: Diagnosis Not Specified

Serious events: 4 serious events

Other events: 11 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: Ewings Sarcoma Primary Cohort n=70 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 1 includes individuals with Ewing's sarcoma who have relapsed within 24 weeks after diagnosis and have received two or more prior chemotherapy regimens.	Cohort 2: Ewings Sarcoma Secondary Cohort n=54 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort n=7 participants at risk Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma n=40 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma n=25 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma n=41 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma n=23 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors n=14 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma n=11 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma n=9 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma n=12 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified n=11 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
Vascular disorders Deep vein thrombosis	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Vascular disorders Haemorrhage	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Vascular disorders Orthostatic hypotension	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Vascular disorders Thrombosis	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Fatigue	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Inflammation	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Oedema peripheral	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Pain	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Pyrexia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Psychiatric disorders Mental status changes	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Nervous system disorders Facial palsy	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Nervous system disorders Somnolence	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Constipation	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Intestinal perforation	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Nausea	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Obstruction gastric	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Vomiting	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Renal and urinary disorders Hydronephrosis	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Endocrine disorders Adrenal haemorrhage	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Dehydration	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Hyperglycaemia	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Pneumonia	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Bacteraemia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Cellulitis	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Device related infection	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Escherichia sepsis	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Infection	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Pyelonephritis	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Sepsis	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Staphylococcal infection	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Urinary tract infection	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.

Other adverse events

Other adverse events
Measure	Cohort 1: Ewings Sarcoma Primary Cohort n=70 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 1 includes individuals with Ewing's sarcoma who have relapsed within 24 weeks after diagnosis and have received two or more prior chemotherapy regimens.	Cohort 2: Ewings Sarcoma Secondary Cohort n=54 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.	Cohort 3: Ewings Sarcoma Expanded Cohort n=7 participants at risk Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.	Cohort 4: Osteosarcoma n=40 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.	Cohort 5: Synovial Sarcoma n=25 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.	Cohort 6: Rhabdomyosarcoma n=41 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.	Cohort 7a: Alveolar Soft Part Sarcoma n=23 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.	Cohort 7b: Desmoplastic Small Round Cell Tumors n=14 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.	Cohort 7c: Extraskeletal Myxoid Chondrosarcoma n=11 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.	Cohort 7d: Clear Cell Sarcoma n=9 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.	Cohort 7e: Myxoid Liposarcoma n=12 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.	Cohort 8: Diagnosis Not Specified n=11 participants at risk Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
Infections and infestations Lower respiratory tract infection	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Cellulitis	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Influenza	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Pharyngitis	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Borrelia infection	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Furuncle	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Rash pustular	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Respiratory tract infection	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Viral infection	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Blood and lymphatic system disorders Neutropenia	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Blood and lymphatic system disorders Leukopenia	4.3% 3/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.5% 5/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Blood and lymphatic system disorders Haemoglobinaemia	7.1% 5/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Blood and lymphatic system disorders Lymphopenia	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	10.0% 4/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Skin and subcutaneous tissue disorders Pruritus	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Skin and subcutaneous tissue disorders Night sweats	4.3% 3/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Skin and subcutaneous tissue disorders Dry skin	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.5% 3/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Skin and subcutaneous tissue disorders Acne	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Skin and subcutaneous tissue disorders Urticaria	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Skin and subcutaneous tissue disorders Decubitus ulcer	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Skin and subcutaneous tissue disorders Skin irritation	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Psychiatric disorders Insomnia	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.4% 4/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.3% 3/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Psychiatric disorders Depression	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.3% 5/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.5% 3/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Psychiatric disorders Mental status changes	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Psychiatric disorders Agitation	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Psychiatric disorders Decreased activity	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Vascular disorders Hypertension	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	27.3% 3/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.7% 2/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Psychiatric disorders Delirium	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Vascular disorders Hot flush	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.5% 3/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Vascular disorders Hypotension	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Vascular disorders Haemorrhage	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Renal and urinary disorders Haematuria	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.3% 3/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Renal and urinary disorders Dysuria	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Renal and urinary disorders Urinary retention	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Renal and urinary disorders Renal failure acute	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Renal and urinary disorders Pollakiuria	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Renal and urinary disorders Urinary incontinence	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Renal and urinary disorders Chromaturia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Injury, poisoning and procedural complications Contusion	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.4% 4/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Injury, poisoning and procedural complications Foreign body	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Injury, poisoning and procedural complications Wound	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Injury, poisoning and procedural complications Joint sprain	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Eye disorders Vision blurred	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Eye disorders Visual impairment	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Eye disorders Diplopia	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Gingival pain	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Eye disorders Dry eye	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Eye disorders Ocular hyperaemia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Ear and labyrinth disorders Ear pain	4.3% 3/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Ear and labyrinth disorders Tinnitus	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Ear and labyrinth disorders Ear discomfort	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Cardiac disorders Tachycardia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Cardiac disorders Pericardia effusion	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Cardiac disorders Sinus tachycardia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Cardiac disorders Palpitations	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Cardiac disorders Pericarditis	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Hepatobiliary disorders Hyperbilirubinaemia	4.3% 3/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Hepatobiliary disorders Liver disorder	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Blood and lymphatic system disorders Thrombocytopenia	12.9% 9/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.4% 4/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.5% 3/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 2/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Reproductive system and breast disorders Vaginal haemorrhage	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Platelet count	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Reproductive system and breast disorders Testicular torsion	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.7% 2/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Wheezing	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Rales	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Hypocalcaemia	5.7% 4/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.7% 2/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Dehydration	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Hypomagnesaemia	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Hyperkalaemia	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Hypoglycaemia	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Hypermagnesaemia	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.7% 4/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.4% 4/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Ascites	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Myalgia	7.1% 5/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Groin pain	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Muscular weakness	5.7% 4/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Bone pain	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.4% 4/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Muscle twitching	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Abdominal pain upper	8.6% 6/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.4% 4/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Dyspepsia	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.5% 3/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Haemorrhoids	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Stomatitis	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Dry mouth	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Dysphagia	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Flatulence	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Abdominal distension	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Faecal incontinence	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Gastritis	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Haematochezia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Toothache	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Gastrointestinal motility disorder	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Proctitis	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Oedema peripheral	4.3% 3/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.5% 3/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.0% 3/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	25.0% 3/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Oedema	5.7% 4/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Chills	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Chest discomfort	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Ulcer	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Hyperthermia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Thirst	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Hypercalcaemia	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Platelet count decreased	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Alanine aminotransferase increased	7.1% 5/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.0% 3/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	17.1% 7/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 2/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.7% 2/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Aspartate aminotransferase increased	11.4% 8/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.4% 4/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.5% 5/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.0% 4/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.2% 5/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	25.0% 3/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Blood alkaline phosphatase increased	11.4% 8/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.5% 5/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Blood lactate dehydrogenase increased	7.1% 5/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.3% 3/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Weight decreased	11.4% 8/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 6/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	15.0% 6/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.8% 4/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	17.4% 4/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.7% 2/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Cough	10.0% 7/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.5% 10/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.5% 9/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	20.0% 5/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.3% 3/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	26.1% 6/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	54.5% 6/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	33.3% 3/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.6% 6/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	24.1% 13/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.5% 5/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.0% 4/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.7% 2/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.3% 5/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.5% 3/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.3% 3/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	17.4% 4/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.1% 5/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 6/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.5% 5/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Blood and lymphatic system disorders Anaemia	11.4% 8/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.3% 5/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	10.0% 4/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.3% 3/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.7% 2/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	27.3% 3/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Nervous system disorders Headache	14.3% 10/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	31.5% 17/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	10.0% 4/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	17.1% 7/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	21.7% 5/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	21.4% 3/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	36.4% 4/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Asthenia	7.1% 5/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.7% 9/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	10.0% 4/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	36.4% 4/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Chest pain	10.0% 7/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	13.0% 7/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	15.0% 6/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.0% 3/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	13.0% 3/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Fatigue	27.1% 19/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	40.7% 22/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	32.5% 13/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.0% 3/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	34.1% 14/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	21.7% 5/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	35.7% 5/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	45.5% 5/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	55.6% 5/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	41.7% 5/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	27.3% 3/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Infusion related reaction	7.1% 5/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	10.0% 4/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.3% 3/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Pain	15.7% 11/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 6/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.8% 4/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 2/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
General disorders Pyrexia	14.3% 10/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	24.1% 13/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.5% 3/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.0% 3/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	26.1% 6/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 2/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Psychiatric disorders Anxiety	5.7% 4/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.5% 5/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.0% 3/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.8% 4/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	21.4% 3/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Abdominal pain	5.7% 4/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.8% 4/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	21.4% 3/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Constipation	17.1% 12/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.5% 10/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	17.5% 7/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.3% 3/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	13.0% 3/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	21.4% 3/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	27.3% 3/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	33.3% 3/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.7% 2/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Diarrhoea	15.7% 11/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	27.8% 15/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	20.0% 8/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.0% 3/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.6% 6/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	30.4% 7/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	27.3% 3/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.7% 2/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Nausea	12.9% 9/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	37.0% 20/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	17.5% 7/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	20.0% 5/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	24.4% 10/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	26.1% 6/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	44.4% 4/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	25.0% 3/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	27.3% 3/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Gastrointestinal disorders Vomiting	15.7% 11/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	20.4% 11/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	20.0% 8/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.0% 4/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	19.5% 8/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	26.1% 6/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	27.3% 3/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Skin and subcutaneous tissue disorders Rash	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 6/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.3% 3/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 2/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Arthralgia	10.0% 7/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 6/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Back pain	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.4% 4/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Muscle spasms	10.0% 7/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.8% 8/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.5% 9/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.6% 6/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	17.4% 4/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	21.4% 3/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.7% 4/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.4% 4/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Musculoskeletal and connective tissue disorders Pain in extremity	7.1% 5/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.3% 5/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.5% 5/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	33.3% 3/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Decreased appetite	18.6% 13/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 12/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	17.1% 7/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 2/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	27.3% 3/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Hyperglycaemia	17.1% 12/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.7% 9/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	12.5% 5/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.0% 4/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.8% 4/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	17.4% 4/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	21.4% 3/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	45.5% 5/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Hypoalbuminaemia	8.6% 6/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.7% 2/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Hypokalaemia	5.7% 4/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	17.4% 4/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Hyponatraemia	8.6% 6/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	13.0% 7/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Metabolism and nutrition disorders Hypophosphataemia	5.7% 4/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	21.7% 5/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Blood creatinine increased	5.7% 4/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.5% 3/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Neutrophil count decreased	4.3% 3/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	14.3% 1/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Blood bilirubin increased	5.7% 4/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Haemoglobin decreased	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.3% 3/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Haemoglobin	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	33.3% 3/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations White blood cell count decreased	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	28.6% 2/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Blood glucose increased	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Transaminases increased	2.9% 2/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Breath sounds abnormal	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Gamma-glutamyltransferase	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Aspartate Aminotransferase	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	22.2% 2/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Blood alkaline phosphatase	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Alanine aminotransferase	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Blood creatinine	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Carbon dioxide decreased	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Neutrophil count	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.3% 1/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations White blood cell count	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.0% 1/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Blood creatine phosphokinase	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Haematocrit	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Protein urine present	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Investigations Urine bilirubin increased	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Nervous system disorders Paraesthesia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.7% 2/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Nervous system disorders Dizziness	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	3.7% 2/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.0% 2/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.0% 2/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.3% 3/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Nervous system disorders Somnolence	5.7% 4/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Nervous system disorders Neuropathy peripheral	4.3% 3/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Nervous system disorders Dysarthria	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Nervous system disorders Dysgeusia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Nervous system disorders Hemiparesis	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Nervous system disorders Syncope	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	1.9% 1/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Nervous system disorders Cerebral ischaemia	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Nervous system disorders Depressed level of consciousness	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Upper respiratory tract infection	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.4% 4/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	8.7% 2/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	7.1% 1/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 1/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	16.7% 2/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Urinary tract infection	0.00% 0/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	11.1% 6/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.9% 2/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
Infections and infestations Nasopharyngitis	1.4% 1/70 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	5.6% 3/54 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/7 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.5% 1/40 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/25 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	2.4% 1/41 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	4.3% 1/23 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/14 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	18.2% 2/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/9 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	0.00% 0/12 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.	9.1% 1/11 • Baseline up to 6 years Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.

Additional Information

Study Director

F. Hoffmann-La Roche AG

Phone: +41 616878333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER