Trial Outcomes & Findings for Long Term Safety and Efficacy Study of Tolebrutinib (SAR442168) in Participants With Relapsing Multiple Sclerosis (NCT NCT03996291)

Last Updated: 2025-10-23

Results Overview

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened or became serious during the respective on-treatment periods.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

125 participants

Primary outcome timeframe

From first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B

Results posted on

2025-10-23

Participant Flow

This long-term study was conducted at 37 centers in 9 countries. Of the 129 participants who completed the parent study DRI15928 (NCT03889639), 126 were screened in this study from 23-Sep-2019 to 10-Mar-2020 of which 1 failed screening due to not meeting eligibility criteria.

A total of 125 participants were treated in this study which consisted of 2 parts: Part A (double-blind) and Part B (open-label). Part A was a short transition period until the dose of tolebrutinib to be used in Phase 3 was determined. In Part B, all participants formed a single dose group (the selected Phase 3 dose).

Participant milestones

Participant milestones
Measure	Part A: Tolebrutinib 5 mg Participants who received tolebrutinib 5 milligrams (mg) orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 15 mg Participants who received tolebrutinib 15 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 30 mg Participants who received tolebrutinib 30 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 60 mg Participants who received tolebrutinib 60 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part B: Tolebrutinib 5/60 mg Participants from Part A: tolebrutinib 5 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 15/60 mg Participants from Part A: tolebrutinib 15 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 30/60 mg Participants from Part A: tolebrutinib 30 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 60/60 mg Participants from Part A: tolebrutinib 60 mg arm who provided consent switched to Part B and continued to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.
Part A (Double-blind Period):39 Weeks STARTED	31	31	32	31	0	0	0	0
Part A (Double-blind Period):39 Weeks COMPLETED	30	31	32	31	0	0	0	0
Part A (Double-blind Period):39 Weeks NOT COMPLETED	1	0	0	0	0	0	0	0
Part B (Open-label Period):222 Weeks STARTED	0	0	0	0	30	31	32	31
Part B (Open-label Period):222 Weeks COMPLETED	0	0	0	0	20	23	20	26
Part B (Open-label Period):222 Weeks NOT COMPLETED	0	0	0	0	10	8	12	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: Tolebrutinib 5 mg Participants who received tolebrutinib 5 milligrams (mg) orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part B: Tolebrutinib 5/60 mg Participants from Part A: tolebrutinib 5 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 15/60 mg Participants from Part A: tolebrutinib 15 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 30/60 mg Participants from Part A: tolebrutinib 30 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 60/60 mg Participants from Part A: tolebrutinib 60 mg arm who provided consent switched to Part B and continued to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.
Part A (Double-blind Period):39 Weeks Other	1	0	0	0	0
Part B (Open-label Period):222 Weeks Poor compliance to protocol	0	0	1	1	0
Part B (Open-label Period):222 Weeks Adverse Event	0	1	0	1	0
Part B (Open-label Period):222 Weeks Other	0	8	7	10	5
Part B (Open-label Period):222 Weeks Withdrawal by Subject	0	1	0	0	0

Baseline Characteristics

Long Term Safety and Efficacy Study of Tolebrutinib (SAR442168) in Participants With Relapsing Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Tolebrutinib 5 mg n=31 Participants Participants who received tolebrutinib 5 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 15 mg n=31 Participants Participants who received tolebrutinib 15 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 30 mg n=32 Participants Participants who received tolebrutinib 30 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 60 mg n=31 Participants Participants who received tolebrutinib 60 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Total n=125 Participants Total of all reporting groups
Age, Continuous	37.1 years STANDARD_DEVIATION 9.9 • n=5 Participants	36.4 years STANDARD_DEVIATION 9.4 • n=7 Participants	40.0 years STANDARD_DEVIATION 9.9 • n=5 Participants	37.8 years STANDARD_DEVIATION 9.0 • n=4 Participants	37.8 years STANDARD_DEVIATION 9.5 • n=21 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	23 Participants n=4 Participants	86 Participants n=21 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants	8 Participants n=4 Participants	39 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	29 Participants n=7 Participants	28 Participants n=5 Participants	28 Participants n=4 Participants	115 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants

PRIMARY outcome

Timeframe: From first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B

Population: The safety population included all participants enrolled in this study and exposed to study drug, regardless of the amount of exposure.

Outcome measures

Outcome measures
Measure	Part A: Tolebrutinib 5 mg n=31 Participants Participants who received tolebrutinib 5 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 15 mg n=31 Participants Participants who received tolebrutinib 15 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 30 mg n=32 Participants Participants who received tolebrutinib 30 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 60 mg n=31 Participants Participants who received tolebrutinib 60 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part B: Tolebrutinib 5/60 mg n=30 Participants Participants from Part A: tolebrutinib 5 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 15/60 mg n=31 Participants Participants from Part A: tolebrutinib 15 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 30/60 mg n=32 Participants Participants from Part A: tolebrutinib 30 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 60/60 mg n=31 Participants Participants from Part A: tolebrutinib 60 mg arm who provided consent switched to Part B and continued to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) TESAEs	0 Participants	2 Participants	1 Participants	2 Participants	5 Participants	3 Participants	3 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) TEAEs	17 Participants	17 Participants	24 Participants	20 Participants	26 Participants	29 Participants	27 Participants	27 Participants

SECONDARY outcome

Timeframe: Weeks 192 and 240

Population: The mITT population included all participants enrolled in this study who had at least 1 day of study drug exposure during study. As pre-specified in protocol and SAP, the main objective of this study was to determine the long-term efficacy of selected Phase 3 dose (60 mg). Part A was a short transition period while picking phase 3 dose; no efficacy analysis was planned for this period alone. Hence, complete efficacy data is presented by LTS16004 dose groups of 5/60, 15/60, 30/60 and 60/60 mg.

Magnetic resonance imaging (MRI) of the brain was performed to identify number of new Gd-enhancing T1-hyperintense lesions. Central review was used to identify new Gd-enhancing T1-hyperintense lesions not present at the previous MRI. mITT=modified intent-to-treat; SAP= statistical analysis plan. Only those participants with data collected at specified timepoints are reported.

Outcome measures

Outcome measures
Measure	Part A: Tolebrutinib 5 mg n=21 Participants Participants who received tolebrutinib 5 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 15 mg n=22 Participants Participants who received tolebrutinib 15 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 30 mg n=19 Participants Participants who received tolebrutinib 30 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 60 mg n=24 Participants Participants who received tolebrutinib 60 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part B: Tolebrutinib 5/60 mg Participants from Part A: tolebrutinib 5 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 15/60 mg Participants from Part A: tolebrutinib 15 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 30/60 mg Participants from Part A: tolebrutinib 30 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 60/60 mg Participants from Part A: tolebrutinib 60 mg arm who provided consent switched to Part B and continued to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.
Mean Number of New Gadolinium (Gd)-Enhancing T1-hyperintense Lesions at Week 240 Relative to Week 192	0.24 number of new Gd-enhancing T1 lesions Standard Deviation 0.54	0.36 number of new Gd-enhancing T1 lesions Standard Deviation 0.66	0.32 number of new Gd-enhancing T1 lesions Standard Deviation 0.75	0.13 number of new Gd-enhancing T1 lesions Standard Deviation 0.45	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 192 and 240

Population: Analysis was performed on the mITT population. As pre-specified in protocol and SAP,main objective of this study was to determine long-term efficacy of selected Phase 3 dose (60 mg).Part A was a short transition period while picking phase 3 dose;no efficacy analysis was planned for this period alone. Hence, complete efficacy data is presented by LTS16004 dose groups of 5/60, 15/60, 30/60, and 60/60 mg. Only those participants with data collected at specified timepoints are reported.

MRI of the brain was performed to identify number of new or enlarging T2 lesions. Central review was used to identify new or enlarging T2 lesions not present at the previous MRI; the values were standardized to per month values by dividing by the number of months (4-week intervals) from the previous MRI to the current MRI.

Outcome measures

Outcome measures
Measure	Part A: Tolebrutinib 5 mg n=21 Participants Participants who received tolebrutinib 5 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 15 mg n=23 Participants Participants who received tolebrutinib 15 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 30 mg n=21 Participants Participants who received tolebrutinib 30 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 60 mg n=26 Participants Participants who received tolebrutinib 60 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part B: Tolebrutinib 5/60 mg Participants from Part A: tolebrutinib 5 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 15/60 mg Participants from Part A: tolebrutinib 15 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 30/60 mg Participants from Part A: tolebrutinib 30 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 60/60 mg Participants from Part A: tolebrutinib 60 mg arm who provided consent switched to Part B and continued to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.
Mean Number of New or Enlarging T2 Lesions at Week 240 Relative to Week 192	0.32 new or enlarging T2 lesions/month Standard Deviation 0.54	0.37 new or enlarging T2 lesions/month Standard Deviation 0.53	0.15 new or enlarging T2 lesions/month Standard Deviation 0.30	0.24 new or enlarging T2 lesions/month Standard Deviation 0.41	—	—	—	—

SECONDARY outcome

Timeframe: Weeks 192 and 240

MRI of the brain was performed to identify number of Gd-enhancing T1-hyperintense lesions. Central review was used to identify Gd-enhancing T1-hyperintense lesions not present at the previous MRI.

Outcome measures

Outcome measures
Measure	Part A: Tolebrutinib 5 mg n=21 Participants Participants who received tolebrutinib 5 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 15 mg n=22 Participants Participants who received tolebrutinib 15 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 30 mg n=19 Participants Participants who received tolebrutinib 30 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 60 mg n=24 Participants Participants who received tolebrutinib 60 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part B: Tolebrutinib 5/60 mg Participants from Part A: tolebrutinib 5 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 15/60 mg Participants from Part A: tolebrutinib 15 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 30/60 mg Participants from Part A: tolebrutinib 30 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 60/60 mg Participants from Part A: tolebrutinib 60 mg arm who provided consent switched to Part B and continued to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.
Total Mean Number of Gd-enhancing T1-hyperintense Lesions at Week 240 Relative to Week 192	0.24 number of Gd-enhancing T1 lesions Standard Deviation 0.54	0.36 number of Gd-enhancing T1 lesions Standard Deviation 0.66	0.37 number of Gd-enhancing T1 lesions Standard Deviation 0.76	0.13 number of Gd-enhancing T1 lesions Standard Deviation 0.45	—	—	—	—

SECONDARY outcome

Timeframe: From Baseline (enrollment in LTS16004, Day 1) to Week 240

Multiple sclerosis (MS) relapse was defined as acute, new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination. Symptoms were attributable to MS, lasted for \>=24 hours with or without recovery, present at normal body temperature and preceded by \>=30 days of clinical stability. ARR was the total number of relapses for participants by dose group divided by the sum of the standardized study duration for participants in the dose group.

Outcome measures

Outcome measures
Measure	Part A: Tolebrutinib 5 mg n=31 Participants Participants who received tolebrutinib 5 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 15 mg n=31 Participants Participants who received tolebrutinib 15 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 30 mg n=32 Participants Participants who received tolebrutinib 30 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 60 mg n=31 Participants Participants who received tolebrutinib 60 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part B: Tolebrutinib 5/60 mg Participants from Part A: tolebrutinib 5 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 15/60 mg Participants from Part A: tolebrutinib 15 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 30/60 mg Participants from Part A: tolebrutinib 30 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 60/60 mg Participants from Part A: tolebrutinib 60 mg arm who provided consent switched to Part B and continued to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.
Annualized Relapse Rate (ARR)	0.26 relapses per participant year Interval 0.15 to 0.46	0.24 relapses per participant year Interval 0.14 to 0.42	0.28 relapses per participant year Interval 0.18 to 0.43	0.23 relapses per participant year Interval 0.13 to 0.38	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of DRI15928) and Week 240

The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal (motor), cerebellar (coordination), sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to MS) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. Baseline assessed for long-term tolebrutinib treatment by change from baseline was defined as the last non-missing value prior to the first administration of randomized study drug in DRI15928 study.

Outcome measures

Outcome measures
Measure	Part A: Tolebrutinib 5 mg n=21 Participants Participants who received tolebrutinib 5 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 15 mg n=23 Participants Participants who received tolebrutinib 15 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 30 mg n=21 Participants Participants who received tolebrutinib 30 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 60 mg n=26 Participants Participants who received tolebrutinib 60 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part B: Tolebrutinib 5/60 mg Participants from Part A: tolebrutinib 5 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 15/60 mg Participants from Part A: tolebrutinib 15 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 30/60 mg Participants from Part A: tolebrutinib 30 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 60/60 mg Participants from Part A: tolebrutinib 60 mg arm who provided consent switched to Part B and continued to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 240	-0.10 score on a scale Standard Deviation 0.96	0.24 score on a scale Standard Deviation 0.95	0.38 score on a scale Standard Deviation 0.69	0.29 score on a scale Standard Deviation 0.70	—	—	—	—

Adverse Events

Part A: Tolebrutinib 5 mg

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Part A: Tolebrutinib 15 mg

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Part A: Tolebrutinib 30 mg

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Part A: Tolebrutinib 60 mg

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Part B: Tolebrutinib 5/60 mg

Serious events: 5 serious events

Other events: 24 other events

Deaths: 0 deaths

Part B: Tolebrutinib 15/60 mg

Serious events: 3 serious events

Other events: 24 other events

Deaths: 0 deaths

Part B: Tolebrutinib 30/60 mg

Serious events: 3 serious events

Other events: 24 other events

Deaths: 0 deaths

Part B: Tolebrutinib 60/60 mg

Serious events: 3 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A: Tolebrutinib 5 mg n=31 participants at risk Participants who received tolebrutinib 5 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 15 mg n=31 participants at risk Participants who received tolebrutinib 15 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 30 mg n=32 participants at risk Participants who received tolebrutinib 30 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 60 mg n=31 participants at risk Participants who received tolebrutinib 60 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part B: Tolebrutinib 5/60 mg n=30 participants at risk Participants from Part A: tolebrutinib 5 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 15/60 mg n=31 participants at risk Participants from Part A: tolebrutinib 15 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 30/60 mg n=32 participants at risk Participants from Part A: tolebrutinib 30 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 60/60 mg n=31 participants at risk Participants from Part A: tolebrutinib 60 mg arm who provided consent switched to Part B and continued to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.
Infections and infestations Appendicitis	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Burn Infection	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Covid-19	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Covid-19 Pneumonia	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Infected Bite	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Postoperative Wound Infection	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Pyelonephritis	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Psychiatric disorders Anxiety	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Nervous system disorders Ischaemic Stroke	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Nervous system disorders Migraine	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Nervous system disorders Multiple Sclerosis Relapse	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Cardiac disorders Supraventricular Tachycardia	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Hepatobiliary disorders Cholelithiasis	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Musculoskeletal and connective tissue disorders Pain In Extremity	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Renal and urinary disorders Nephrolithiasis	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Reproductive system and breast disorders Ovarian Haemorrhage	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.7% 2/30 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Reproductive system and breast disorders Uterine Polyp	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Investigations Haemoglobin Decreased	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Injury, poisoning and procedural complications Joint Dislocation	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.

Other adverse events

Other adverse events
Measure	Part A: Tolebrutinib 5 mg n=31 participants at risk Participants who received tolebrutinib 5 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 15 mg n=31 participants at risk Participants who received tolebrutinib 15 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 30 mg n=32 participants at risk Participants who received tolebrutinib 30 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part A: Tolebrutinib 60 mg n=31 participants at risk Participants who received tolebrutinib 60 mg orally once daily in the parent study continued to receive the same dose until the dose of tolebrutinib to be used in Phase 3 was determined.	Part B: Tolebrutinib 5/60 mg n=30 participants at risk Participants from Part A: tolebrutinib 5 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 15/60 mg n=31 participants at risk Participants from Part A: tolebrutinib 15 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 30/60 mg n=32 participants at risk Participants from Part A: tolebrutinib 30 mg arm who provided consent switched to Part B to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.	Part B: Tolebrutinib 60/60 mg n=31 participants at risk Participants from Part A: tolebrutinib 60 mg arm who provided consent switched to Part B and continued to receive the selected Phase 3 dose of tolebrutinib 60 mg orally once daily until Month 60.
Injury, poisoning and procedural complications Foot Fracture	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Gastrointestinal disorders Enteritis	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Gastrointestinal disorders Toothache	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Covid-19	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	33.3% 10/30 • Number of events 10 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	32.3% 10/31 • Number of events 12 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	21.9% 7/32 • Number of events 9 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	45.2% 14/31 • Number of events 20 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Cystitis	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	9.4% 3/32 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Cystitis Bacterial	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	9.4% 3/32 • Number of events 7 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	16.1% 5/31 • Number of events 14 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Influenza	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Nasopharyngitis	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	9.4% 3/32 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	16.7% 5/30 • Number of events 7 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	19.4% 6/31 • Number of events 11 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	12.5% 4/32 • Number of events 6 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	19.4% 6/31 • Number of events 12 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Pharyngitis	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	12.9% 4/31 • Number of events 4 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.2% 2/32 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Sinusitis	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.2% 2/32 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Tonsillitis	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 4 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	12.9% 4/31 • Number of events 4 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	12.5% 4/32 • Number of events 7 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	9.7% 3/31 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Urinary Tract Infection	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	15.6% 5/32 • Number of events 6 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	9.7% 3/31 • Number of events 5 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Gastrointestinal disorders Haemorrhoids	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Urinary Tract Infection Bacterial	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	9.4% 3/32 • Number of events 4 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Infections and infestations Viral Upper Respiratory Tract Infection	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	16.1% 5/31 • Number of events 5 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	10.0% 3/30 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	9.4% 3/32 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	12.9% 4/31 • Number of events 4 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Immune system disorders Seasonal Allergy	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.7% 2/30 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.2% 2/32 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Metabolism and nutrition disorders Obesity	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.7% 2/30 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Psychiatric disorders Anxiety	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.2% 2/32 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Psychiatric disorders Insomnia	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.2% 2/32 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Nervous system disorders Carpal Tunnel Syndrome	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Nervous system disorders Dizziness	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Nervous system disorders Headache	9.7% 3/31 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	12.5% 4/32 • Number of events 4 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	9.7% 3/31 • Number of events 4 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.7% 2/30 • Number of events 4 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.2% 2/32 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	9.7% 3/31 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Nervous system disorders Migraine	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.2% 2/32 • Number of events 4 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Nervous system disorders Tension Headache	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Vascular disorders Hypertension	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	12.5% 4/32 • Number of events 4 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.7% 2/30 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Gastrointestinal disorders Abdominal Pain Upper	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	9.7% 3/31 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Gastrointestinal disorders Diarrhoea	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.7% 2/30 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Gastrointestinal disorders Dyspepsia	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.2% 2/32 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Gastrointestinal disorders Nausea	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	10.0% 3/30 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Skin and subcutaneous tissue disorders Dry Skin	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Musculoskeletal and connective tissue disorders Arthralgia	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.2% 2/32 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	16.1% 5/31 • Number of events 5 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	20.0% 6/30 • Number of events 7 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	16.1% 5/31 • Number of events 7 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	9.7% 3/31 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Musculoskeletal and connective tissue disorders Muscular Weakness	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	9.7% 3/31 • Number of events 4 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	9.7% 3/31 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Musculoskeletal and connective tissue disorders Pain In Extremity	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 3 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Renal and urinary disorders Nephrolithiasis	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Renal and urinary disorders Renal Colic	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.2% 2/32 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
General disorders Asthenia	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.2% 2/32 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
General disorders Pyrexia	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.2% 2/32 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Injury, poisoning and procedural complications Contusion	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
Injury, poisoning and procedural complications Fall	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.2% 2/32 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
General disorders Fatigue	3.2% 1/31 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.2% 1/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/30 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.
General disorders Influenza Like Illness	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/32 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.3% 1/30 • Number of events 1 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	6.5% 2/31 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	3.1% 1/32 • Number of events 2 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.	0.00% 0/31 • Adverse events were collected from first dose of study drug (Day 1) up to maximum exposure, 39 weeks in Part A and 222 weeks in Part B. All-cause mortality (deaths) was collected from signing informed consent form (Week -6) up to end of follow-up, approximately 62 months Analysis was performed on the safety population.

Additional Information

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