Trial Outcomes & Findings for A Study to Assess the Safety, Tolerability, and Effect on Disease Progression of BIIB105 in Participants With Amyotrophic Lateral Sclerosis (ALS) and Participants With the ALS Ataxin-2 (ATXN2) Genetic Mutation (NCT NCT04494256)

Last Updated: 2025-10-09

Results Overview

An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event. A TEAE/TESAE was defined as any AE/SAE with an onset date that is on or after the first dose of study drug or any pre-existing condition that has worsened in severity after the first dose of study drug.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

99 participants

Primary outcome timeframe

From first dose of the study drug in Part 1 up to end of follow up period in Part 1 (up to Day 260)

Results posted on

2025-10-09

Participant Flow

Participants diagnosed with amyotrophic lateral sclerosis (ALS) and ALS associated with ataxin-2 (ATXN2) polyCAG expansion (polyQALS) took part in the study at investigational sites in the United States, Netherlands, Canada and Italy from 28 September 2020 to 13 August 2024.

A total of 99 participants were randomized in Part 1 (placebo-controlled) of study to receive BIIB105 or placebo, of which 80 participants completed Part 1. A total of 70 eligible participants who completed Part 1 were enrolled into Part 2 (open-label) of study to receive BIIB105. Part 2 of study was terminated early based on Sponsor's decision.

Participant milestones

Participant milestones
Measure	Part 1: Pooled Placebo 1+2 Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 Milligrams (mg) Participants with ALS received 3 loading doses of BIIB105 5mg, intrathecally (IT), administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg Participants with ALS received 3 loading doses of BIIB105 20mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 2: BIIB105 60 mg Participants from cohorts A-C2, who received 5, 20 and 60 mg doses of BIIB105 and placebo in Part 1 and completed Week 25 (Day 175) visit in Part 1 received BIIB105 60 mg in Part 2.	Part 2: BIIB105 120 mg Participants from Cohorts D1 and D2 who received 120 mg dose of BIIB105 and placebo in Part 1 and completed Week 25 (Day 176) visit in Part 1 received BIIB105 120 mg in Part 2.
Part 1: Double Blinded Period STARTED	28	6	6	11	48	0	0
Part 1: Double Blinded Period COMPLETED	26	6	5	9	34	0	0
Part 1: Double Blinded Period NOT COMPLETED	2	0	1	2	14	0	0
Part 2: Open Label Period STARTED	0	0	0	0	0	19	51
Part 2: Open Label Period COMPLETED	0	0	0	0	0	0	0
Part 2: Open Label Period NOT COMPLETED	0	0	0	0	0	19	51

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: Pooled Placebo 1+2 Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort B: BIIB105 20 mg Participants with ALS received 3 loading doses of BIIB105 20mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 2: BIIB105 60 mg Participants from cohorts A-C2, who received 5, 20 and 60 mg doses of BIIB105 and placebo in Part 1 and completed Week 25 (Day 175) visit in Part 1 received BIIB105 60 mg in Part 2.	Part 2: BIIB105 120 mg Participants from Cohorts D1 and D2 who received 120 mg dose of BIIB105 and placebo in Part 1 and completed Week 25 (Day 176) visit in Part 1 received BIIB105 120 mg in Part 2.
Part 1: Double Blinded Period Adverse Event	1	0	0	3	0	0
Part 1: Double Blinded Period Disease Progression - As Defined by the Protocol	0	0	0	5	0	0
Part 1: Double Blinded Period Protocol Deviation	0	0	0	1	0	0
Part 1: Double Blinded Period SubjectWithdrawal-VisitBurden/SchedulingConflict	0	0	1	3	0	0
Part 1: Double Blinded Period Withdrawal by Subject - Other	1	1	1	1	0	0
Part 1: Double Blinded Period Reason Not Specified	0	0	0	1	0	0
Part 2: Open Label Period Death	0	0	0	0	4	2
Part 2: Open Label Period Adverse Event	0	0	0	0	0	2
Part 2: Open Label Period Disease Progression - As Defined by the Protocol	0	0	0	0	5	6
Part 2: Open Label Period Lack of Efficacy - Based on Subject Perception	0	0	0	0	0	1
Part 2: Open Label Period Study Terminated by Sponsor	0	0	0	0	4	35
Part 2: Open Label Period SubjectWithdrawal-VisitBurden/SchedulingConflict	0	0	0	0	5	4
Part 2: Open Label Period Withdrawal by Subject - Other	0	0	0	0	1	1

Baseline Characteristics

A Study to Assess the Safety, Tolerability, and Effect on Disease Progression of BIIB105 in Participants With Amyotrophic Lateral Sclerosis (ALS) and Participants With the ALS Ataxin-2 (ATXN2) Genetic Mutation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Pooled Placebo 1+2 n=28 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=6 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg n=6 Participants Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg n=11 Participants Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg n=48 Participants Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Total n=99 Participants Total of all reporting groups
Age, Continuous	59.9 years STANDARD_DEVIATION 11.15 • n=99 Participants	60.5 years STANDARD_DEVIATION 5.72 • n=107 Participants	49.3 years STANDARD_DEVIATION 17.84 • n=206 Participants	53.3 years STANDARD_DEVIATION 12.77 • n=7 Participants	57.7 years STANDARD_DEVIATION 11.45 • n=31 Participants	57.5 years STANDARD_DEVIATION 11.83 • n=30 Participants
Sex: Female, Male Female	9 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants	3 Participants n=7 Participants	14 Participants n=31 Participants	31 Participants n=30 Participants
Sex: Female, Male Male	19 Participants n=99 Participants	4 Participants n=107 Participants	3 Participants n=206 Participants	8 Participants n=7 Participants	34 Participants n=31 Participants	68 Participants n=30 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants	1 Participants n=7 Participants	3 Participants n=31 Participants	10 Participants n=30 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=99 Participants	6 Participants n=107 Participants	4 Participants n=206 Participants	10 Participants n=7 Participants	45 Participants n=31 Participants	88 Participants n=30 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	1 Participants n=30 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants	1 Participants n=30 Participants
Race/Ethnicity, Customized Asian	3 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants	4 Participants n=30 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=99 Participants	00 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants	1 Participants n=30 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants	1 Participants n=30 Participants
Race/Ethnicity, Customized White	22 Participants n=99 Participants	6 Participants n=107 Participants	5 Participants n=206 Participants	10 Participants n=7 Participants	40 Participants n=31 Participants	83 Participants n=30 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants	1 Participants n=30 Participants
Race/Ethnicity, Customized Not reported due to confidentiality regulations	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	1 Participants n=30 Participants
Race/Ethnicity, Customized Other	2 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants	3 Participants n=31 Participants	7 Participants n=30 Participants

PRIMARY outcome

Timeframe: From first dose of the study drug in Part 1 up to end of follow up period in Part 1 (up to Day 260)

Population: Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=28 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=6 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg n=6 Participants Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg n=11 Participants Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg n=48 Participants Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) TEAEs	28 Participants	6 Participants	6 Participants	11 Participants	48 Participants
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) TESAEs	5 Participants	0 Participants	0 Participants	1 Participants	7 Participants

PRIMARY outcome

Timeframe: From first dose of the study in Part 2 up to end of follow up period in Part 2 (up to Day 1184)

Population: Part 2 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 2.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=19 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=51 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Part 2: Number of Participants With TEAEs and TESAEs TEAEs	19 Participants	49 Participants	—	—	—
Part 2: Number of Participants With TEAEs and TESAEs TESAEs	7 Participants	14 Participants	—	—	—

SECONDARY outcome

Timeframe: Pre-dose and 1, 2, 4, 6 hours post-dose on days 1, 15, 29, 57, 85,113, 141, 169 and on days 2, 8, 92, and 176

Population: The Part 1 pharmacokinetic (PK) analysis population included all randomized participants who received at least 1 dose of study treatment and had at least 1 postdose serum and/or cerebrospinal fluid (CSF) BIIB105 measurement in Part 1. 'Number analyzed (n)' signifies number of participants evaluable for this outcome measure (OM) at the specified timepoint.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=6 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=6 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg n=11 Participants Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg n=48 Participants Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Part 1: Serum Concentrations of BIIB105 Day 1: Pre-dose	0.00 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 0.00	0.00 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 0.00	0.00 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 0.00	0.00 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 0.00	—
Part 1: Serum Concentrations of BIIB105 Day 1: 1 HR post-dose	7.21 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 500.18	57.70 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 285.30	34.98 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 465.78	187.14 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 351.05	—
Part 1: Serum Concentrations of BIIB105 Day 1: 2 HR post-dose	32.20 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 177.01	135.71 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 109.27	250.28 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 101.57	620.38 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 132.37	—
Part 1: Serum Concentrations of BIIB105 Day 1: 4 HR post-dose	41.38 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 125.95	211.34 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 68.29	488.11 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 51.22	798.21 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 86.03	—
Part 1: Serum Concentrations of BIIB105 Day 1: 6 HR post-dose	39.27 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 102.97	165.05 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 60.63	528.45 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 61.49	774.73 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 60.51	—
Part 1: Serum Concentrations of BIIB105 Day 2	6.76 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 65.90	29.07 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 76.82	118.70 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 103.89	260.03 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 67.59	—
Part 1: Serum Concentrations of BIIB105 Day 8	0.46 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 18.74	0.47 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 36.02	1.38 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 74.15	2.97 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 43.60	—
Part 1: Serum Concentrations of BIIB105 Day 15: 1 HR post-dose	3.85 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 172.70	22.24 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 226.26	56.01 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 489.04	257.73 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 290.21	—
Part 1: Serum Concentrations of BIIB105 Day 29: 1 HR post-dose	5.80 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 117.90	16.45 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 557.48	114.69 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 226.87	248.00 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 152.63	—
Part 1: Serum Concentrations of BIIB105 Day 29: 6 HR post-dose	33.28 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 127.43	151.47 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 87.99	555.65 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 52.83	942.06 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 69.00	—
Part 1: Serum Concentrations of BIIB105 Day 57: Pre-dose	0.00 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 0.00	0.41 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 21.53	0.79 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 80.26	1.83 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 69.80	—
Part 1: Serum Concentrations of BIIB105 Day 57: 1 HR post-dose	7.45 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 275.61	7.98 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 159.54	44.33 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 615.14	227.06 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 214.59	—
Part 1: Serum Concentrations of BIIB105 Day 57: 2 HR post-dose	22.05 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 153.51	26.59 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 107.62	274.02 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 128.39	713.36 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 122.48	—
Part 1: Serum Concentrations of BIIB105 Day 57: 4 HR post-dose	27.72 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 123.67	74.60 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 85.53	471.12 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 95.76	887.82 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 105.32	—
Part 1: Serum Concentrations of BIIB105 Day 85: 2 HR post-dose	20.60 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 95.33	69.04 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 265.82	248.33 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 84.14	651.00 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 127.92	—
Part 1: Serum Concentrations of BIIB105 Day 85: 4 HR post-dose	27.69 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 111.28	140.04 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 91.00	416.74 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 80.90	799.70 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 89.26	—
Part 1: Serum Concentrations of BIIB105 Day 141: 4 HR post-dose	—	—	—	1044.80 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 101.09	—
Part 1: Serum Concentrations of BIIB105 Day 141: 6 HR post-dose	—	—	—	996.44 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 85.54	—
Part 1: Serum Concentrations of BIIB105 Day 169: Pre-dose	—	—	—	2.95 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 153.02	—
Part 1: Serum Concentrations of BIIB105 Day 169: 1 HR post-dose	—	—	—	288.75 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 217.19	—
Part 1: Serum Concentrations of BIIB105 Day 15: Pre-dose	0.00 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 0.00	0.50 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 20.12	0.78 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 52.94	1.90 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 43.15	—
Part 1: Serum Concentrations of BIIB105 Day 15: 2 HR post-dose	16.89 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 111.49	94.51 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 140.45	246.73 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 142.61	972.44 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 110.25	—
Part 1: Serum Concentrations of BIIB105 Day 15: 4 HR post-dose	30.07 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 74.48	139.75 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 137.49	363.86 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 77.37	996.20 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 83.48	—
Part 1: Serum Concentrations of BIIB105 Day 15: 6 HR post-dose	27.28 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 106.96	139.00 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 98.33	411.61 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 49.33	897.25 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 78.56	—
Part 1: Serum Concentrations of BIIB105 Day 29: Pre-dose	0.45 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 24.48	0.48 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 28.47	1.23 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 64.84	2.59 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 59.99	—
Part 1: Serum Concentrations of BIIB105 Day 29: 2 HR post-dose	16.53 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 121.68	51.58 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 602.03	420.39 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 116.92	773.11 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 95.92	—
Part 1: Serum Concentrations of BIIB105 Day 29: 4 HR post-dose	31.29 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 120.91	102.80 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 200.28	566.43 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 71.83	953.50 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 80.75	—
Part 1: Serum Concentrations of BIIB105 Day 57: 6 HR post-dose	27.33 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 105.30	89.38 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 74.82	416.91 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 94.12	889.54 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 89.20	—
Part 1: Serum Concentrations of BIIB105 Day 85: Pre-dose	0.50 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 0.00	0.40 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 33.26	0.74 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 64.453	1.91 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 113.18	—
Part 1: Serum Concentrations of BIIB105 Day 85: 1 HR post-dose	7.02 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 111.81	18.91 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 240.40	77.63 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 142.75	231.31 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 236.91	—
Part 1: Serum Concentrations of BIIB105 Day 85: 6 HR post-dose	29.83 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 119.17	140.74 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 50.95	453.58 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 74.39	837.50 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 73.65	—
Part 1: Serum Concentrations of BIIB105 Day 92	0.43 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 23.54	0.56 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 47.98	2.05 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 92.02	4.47 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 64.10	—
Part 1: Serum Concentrations of BIIB105 Day 113: Pre-dose	—	—	—	1.95 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 59.79	—
Part 1: Serum Concentrations of BIIB105 Day 113: 1 HR post-dose	—	—	—	193.04 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 198.68	—
Part 1: Serum Concentrations of BIIB105 Day 113: 2 HR post-dose	—	—	—	632.28 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 91.07	—
Part 1: Serum Concentrations of BIIB105 Day 113: 4 HR post-dose	—	—	—	802.46 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 91.76	—
Part 1: Serum Concentrations of BIIB105 Day 113: 6 HR post-dose	—	—	—	858.58 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 86.76	—
Part 1: Serum Concentrations of BIIB105 Day 141: Pre-dose	—	—	—	2.07 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 80.82	—
Part 1: Serum Concentrations of BIIB105 Day 141: 1 HR post-dose	—	—	—	457.25 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 162.57	—
Part 1: Serum Concentrations of BIIB105 Day 141: 2 HR post-dose	—	—	—	949.31 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 120.40	—
Part 1: Serum Concentrations of BIIB105 Day 169: 2 HR post-dose	—	—	—	702.24 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 107.10	—
Part 1: Serum Concentrations of BIIB105 Day 169: 4 HR post-dose	—	—	—	816.90 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 86.61	—
Part 1: Serum Concentrations of BIIB105 Day 169: 6 HR post-dose	—	—	—	683.89 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 158.85	—
Part 1: Serum Concentrations of BIIB105 Day 176	—	—	—	6.97 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 132.41	—

SECONDARY outcome

Timeframe: Pre-dose on Days 1, 15, 29, 57, 85, 113, 141, 169, and on days 92, 130, 175, and 176

Population: The Part 1 PK analysis population included all randomized participants who received at least 1 dose of study treatment and had at least 1 postdose serum and/or CSF BIIB105 measurement in Part 1. 'Number analyzed (n)' signifies number of participants evaluable for this OM at the specified time point.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=6 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=6 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg n=11 Participants Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg n=48 Participants Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Part 1: CSF Concentrations of BIIB105 Day 85 : Pre-dose	2.37 ng/mL Geometric Coefficient of Variation 30.35	3.18 ng/mL Geometric Coefficient of Variation 72.73	6.50 ng/mL Geometric Coefficient of Variation 36.23	14.06 ng/mL Geometric Coefficient of Variation 77.42	—
Part 1: CSF Concentrations of BIIB105 Day 92	5.01 ng/mL Geometric Coefficient of Variation 30.62	6.28 ng/mL Geometric Coefficient of Variation 74.45	25.51 ng/mL Geometric Coefficient of Variation 66.26	—	—
Part 1: CSF Concentrations of BIIB105 Day 113	—	—	—	17.08 ng/mL Geometric Coefficient of Variation 86.41	—
Part 1: CSF Concentrations of BIIB105 Day 130	2.09 ng/mL Geometric Coefficient of Variation 32.22	2.45 ng/mL Geometric Coefficient of Variation 57.06	5.42 ng/mL Geometric Coefficient of Variation 40.72	—	—
Part 1: CSF Concentrations of BIIB105 Day 141	—	—	—	17.91 ng/mL Geometric Coefficient of Variation 84.83	—
Part 1: CSF Concentrations of BIIB105 Day 169	—	—	—	18.88 ng/mL Geometric Coefficient of Variation 74.23	—
Part 1: CSF Concentrations of BIIB105 Day 175	1.16 ng/mL Geometric Coefficient of Variation 54.77	1.16 ng/mL Geometric Coefficient of Variation 36.06	2.68 ng/mL Geometric Coefficient of Variation 46.05	—	—
Part 1: CSF Concentrations of BIIB105 Day 176	—	—	—	17.35 ng/mL Geometric Coefficient of Variation 0.04	—
Part 1: CSF Concentrations of BIIB105 Day 1 : Pre-dose	0.00 ng/mL Geometric Coefficient of Variation 0.00	0.00 ng/mL Geometric Coefficient of Variation 0.00	0.00 ng/mL Geometric Coefficient of Variation 0.00	0.00 ng/mL Geometric Coefficient of Variation 0.00	—
Part 1: CSF Concentrations of BIIB105 Day 15 : Pre-dose	1.93 ng/mL Geometric Coefficient of Variation 41.54	2.71 ng/mL Geometric Coefficient of Variation 55.21	5.75 ng/mL Geometric Coefficient of Variation 62.33	14.54 ng/mL Geometric Coefficient of Variation 82.48	—
Part 1: CSF Concentrations of BIIB105 Day 29 : Pre-dose	3.53 ng/mL Geometric Coefficient of Variation 33.52	4.32 ng/mL Geometric Coefficient of Variation 52.42	11.53 ng/mL Geometric Coefficient of Variation 49.38	17.53 ng/mL Geometric Coefficient of Variation 95.18	—
Part 1: CSF Concentrations of BIIB105 Day 57 : Pre-dose	2.32 ng/mL Geometric Coefficient of Variation 28.96	2.65 ng/mL Geometric Coefficient of Variation 46.23	4.82 ng/mL Geometric Coefficient of Variation 59.33	10.29 ng/mL Geometric Coefficient of Variation 79.90	—

SECONDARY outcome

Timeframe: Day 1

Population: Part 1 PK analysis population included all randomized participants who received at least 1 dose of study treatment and had at least 1 postdose serum and/or CSF BIIB105 measurement in Part 1. 'Overall number of participants analyzed' signifies number of participants with data available for OM analysis.

AUCinf is the area under the serum concentration-time profile from time 0 extrapolated to infinite time. AUCinf was reported following dose 1 as planned.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=2 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=5 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg n=10 Participants Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg n=42 Participants Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUCinf)	934.22 Hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 52.89	3546.89 Hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 53.50	11258.45 Hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 14.57	24466.44 Hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 30.24	—

SECONDARY outcome

Timeframe: Day 1

AUClast was reported following dose 1 as planned.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=6 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=6 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg n=11 Participants Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg n=44 Participants Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast)	574.59 h*ng/mL Geometric Coefficient of Variation 79.16	3239.40 h*ng/mL Geometric Coefficient of Variation 52.73	11758.68 h*ng/mL Geometric Coefficient of Variation 21.12	24289.70 h*ng/mL Geometric Coefficient of Variation 30.50	—

SECONDARY outcome

Timeframe: Days 1, 15, 29, 57, 85, 113, 141 and 169

Population: Part 1 PK analysis population included all randomized participants who received at least 1 dose of study treatment and had at least 1 postdose serum and/or CSF BIIB105 measurement in Part 1. 'Number analyzed (n)' signifies number of participants evaluable for this OM at the specified timepoint.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=6 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=6 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg n=11 Participants Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg n=48 Participants Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Part 1: Maximum Observed Serum Concentration (Cmax) Day 1	52.18 ng/mL Geometric Coefficient of Variation 123.13	227.80 ng/mL Geometric Coefficient of Variation 73.20	644.10 ng/mL Geometric Coefficient of Variation 55.31	1019.11 ng/mL Geometric Coefficient of Variation 76.61	—
Part 1: Maximum Observed Serum Concentration (Cmax) Day 15	31.03 ng/mL Geometric Coefficient of Variation 78.23	165.37 ng/mL Geometric Coefficient of Variation 118.45	495.03 ng/mL Geometric Coefficient of Variation 76.73	1312.42 ng/mL Geometric Coefficient of Variation 93.96	—
Part 1: Maximum Observed Serum Concentration (Cmax) Day 29	34.11 ng/mL Geometric Coefficient of Variation 119.62	164.15 ng/mL Geometric Coefficient of Variation 101.46	616.02 ng/mL Geometric Coefficient of Variation 61.54	1173.71 ng/mL Geometric Coefficient of Variation 75.74	—
Part 1: Maximum Observed Serum Concentration (Cmax) Day 57	31.92 ng/mL Geometric Coefficient of Variation 136.57	94.60 ng/mL Geometric Coefficient of Variation 75.30	513.84 ng/mL Geometric Coefficient of Variation 98.01	1052.70 ng/mL Geometric Coefficient of Variation 99.57	—
Part 1: Maximum Observed Serum Concentration (Cmax) Day 85	31.43 ng/mL Geometric Coefficient of Variation 117.43	168.38 ng/mL Geometric Coefficient of Variation 59.96	476.91 ng/mL Geometric Coefficient of Variation 75.87	1009.44 ng/mL Geometric Coefficient of Variation 84.68	—
Part 1: Maximum Observed Serum Concentration (Cmax) Day 113	—	—	—	949.58 ng/mL Geometric Coefficient of Variation 83.69	—
Part 1: Maximum Observed Serum Concentration (Cmax) Day 141	—	—	—	1243.75 ng/mL Geometric Coefficient of Variation 91.13	—
Part 1: Maximum Observed Serum Concentration (Cmax) Day 169	—	—	—	957.24 ng/mL Geometric Coefficient of Variation 86.51	—

SECONDARY outcome

Timeframe: Days 1, 15, 29, 57, 85, 113, 141 and 169

Population: Part 1 PK analysis population included all randomized participants who received at least 1 dose of study treatment and had at least 1 postdose serum and/or CSF BIIB105 measurement in Part 1. 'Number analyzed (n)' signifies number of participants evaluable for this OM at the specified timepoint.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=6 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=6 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg n=11 Participants Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg n=48 Participants Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) Day 15	5.0 hour Interval 4.0 to 6.0	5.0 hour Interval 2.0 to 6.0	5.9 hour Interval 2.0 to 6.0	4.1 hour Interval 1.0 to 6.0	—
Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) Day 29	5.8 hour Interval 4.0 to 6.0	5.8 hour Interval 2.0 to 6.0	4.2 hour Interval 2.0 to 6.0	4.1 hour Interval 2.0 to 6.0	—
Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) Day 57	5.8 hour Interval 2.0 to 6.0	5.0 hour Interval 4.0 to 6.0	4.2 hour Interval 1.0 to 6.0	4.5 hour Interval 1.0 to 6.0	—
Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) Day 85	5.1 hour Interval 4.0 to 6.0	4.3 hour Interval 4.0 to 6.0	5.8 hour Interval 4.0 to 6.0	5.8 hour Interval 2.0 to 6.0	—
Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) Day 1	4.2 hour Interval 2.0 to 6.0	4.2 hour Interval 2.0 to 6.0	5.8 hour Interval 2.0 to 23.0	4.3 hour Interval 1.0 to 24.0	—
Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) Day 113	—	—	—	5.3 hour Interval 1.0 to 6.0	—
Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) Day 141	—	—	—	4.0 hour Interval 1.0 to 6.0	—
Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) Day 169	—	—	—	4.1 hour Interval 1.0 to 6.0	—

SECONDARY outcome

Timeframe: Day 1

Population: Part 1 PK analysis population included all randomized participants who received at least 1 dose of study treatment and had at least 1 postdose serum and/or CSF BIIB105 measurement in Part 1. ''Overall number of participants (n)' signifies number of participants evaluable for this OM.

Elimination half-life (t1/2) was reported following dose 1 as planned.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=2 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=5 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg n=10 Participants Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg n=42 Participants Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Part 1: Elimination Half-Life (t1/2) in Serum	14.0 hour Interval 5.0 to 23.0	26.6 hour Interval 17.0 to 62.0	41.7 hour Interval 33.0 to 62.0	39.8 hour Interval 22.0 to 82.0	—

SECONDARY outcome

Timeframe: Days 29, 57, 85, 113, 130 (For cohorts A, B, C1 and C2)/141 (For cohorts D1 and D2), 169 (For cohorts A, B, C1 and C2)/175 (For cohorts D1 and D2) and 241

Population: The Part 1 pharmacodynamic (PD) population included participants who received at least 1 dose of study treatment and have at least 1 available postdose evaluation of the respective PD endpoint in the study in Part 1. 'Number analyzed (n)' indicates the number of participants evaluable for the OM at the specified timepoint.

Plasma NfL ratio to baseline was reported in terms of geometric mean ratio.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=28 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=6 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg n=6 Participants Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg n=11 Participants Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg n=47 Participants Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 29	1.04 ratio Geometric Coefficient of Variation 20.32	1.05 ratio Geometric Coefficient of Variation 8.47	0.83 ratio Geometric Coefficient of Variation 47.1	1.06 ratio Geometric Coefficient of Variation 11.23	1.15 ratio Geometric Coefficient of Variation 72.72
Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 57	1.08 ratio Geometric Coefficient of Variation 19.91	0.95 ratio Geometric Coefficient of Variation 14.63	0.97 ratio Geometric Coefficient of Variation 15.95	1.08 ratio Geometric Coefficient of Variation 20.43	1.03 ratio Geometric Coefficient of Variation 21.7
Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 85	0.99 ratio Geometric Coefficient of Variation 17.27	0.99 ratio Geometric Coefficient of Variation 15.7	0.98 ratio Geometric Coefficient of Variation 26.4	1.11 ratio Geometric Coefficient of Variation 19.85	0.99 ratio Geometric Coefficient of Variation 19.62
Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 113	1.06 ratio Geometric Coefficient of Variation 19.95	—	—	—	1.01 ratio Geometric Coefficient of Variation 21.77
Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 130 (A,B,C1,C2)/Day 141 (D1,D2)	1.09 ratio Geometric Coefficient of Variation 20.46	1.10 ratio Geometric Coefficient of Variation 8.58	0.92 ratio Geometric Coefficient of Variation 40.79	0.99 ratio Geometric Coefficient of Variation 30.8	1.03 ratio Geometric Coefficient of Variation 41.35
Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 169 (A,B,C1,C2)/Day 175 (D1,D2)	1.10 ratio Geometric Coefficient of Variation 23.67	1.02 ratio Geometric Coefficient of Variation 22.58	1.10 ratio Geometric Coefficient of Variation 24.55	1.08 ratio Geometric Coefficient of Variation 29.73	1.06 ratio Geometric Coefficient of Variation 24.92
Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 214	—	—	—	—	1.07 ratio

SECONDARY outcome

Timeframe: Predose on Days 1,15,29,57,85 and on Days 1,15,29,57,85,113,141,169.176,197,210,225,253,281,309,337,365,393,420,448,476,504,532,560,588,616,644,672,700,726,728

Population: Integrated Part 1 \& 2=Part 1 PK population.Overall number of participants analyzed=number of participants evaluable for OM analysis.Number analyzed=number of participants evaluable at specified timepoint.Assessment was planned upto Day 1093 however,no assessments were conducted after Day 729 due to early termination.Treatment groups for integrated analysis of Parts 1 \& 2 were planned for Early-start BIIB105 120 mg \& Placebo/Delayed-start BIIB105,\& results are reported for these treatment groups.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=48 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=17 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 15	31.04 ng/mL	12.93 ng/mL Geometric Coefficient of Variation 70.31	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 29: Pre-dose	17.53 ng/mL Geometric Coefficient of Variation 95.18	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 29	—	18.62 ng/mL Geometric Coefficient of Variation 93.41	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 57 : Pre-dose	10.29 ng/mL Geometric Coefficient of Variation 79.90	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 57	—	9.72 ng/mL Geometric Coefficient of Variation 49.08	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 85 : Pre-dose	14.06 ng/mL Geometric Coefficient of Variation 77.42	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 85	—	14.54 ng/mL Geometric Coefficient of Variation 63.76	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 113	17.08 ng/mL Geometric Coefficient of Variation 86.41	20.70 ng/mL Geometric Coefficient of Variation 56.82	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 141	17.91 ng/mL Geometric Coefficient of Variation 84.83	24.50 ng/mL Geometric Coefficient of Variation 30.13	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 169	18.88 ng/mL Geometric Coefficient of Variation 74.23	19.32 ng/mL Geometric Coefficient of Variation 36.08	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 176	17.35 ng/mL Geometric Coefficient of Variation 0.04	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 197	24.88 ng/mL Geometric Coefficient of Variation 57.69	24.99 ng/mL Geometric Coefficient of Variation 71.18	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 225	24.14 ng/mL Geometric Coefficient of Variation 63.21	30.52 ng/mL Geometric Coefficient of Variation 13.97	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 253	23.54 ng/mL Geometric Coefficient of Variation 62.86	21.68 ng/mL Geometric Coefficient of Variation 70.34	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 309	27.14 ng/mL Geometric Coefficient of Variation 63.54	30.47 ng/mL Geometric Coefficient of Variation 13.01	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 337	31.34 ng/mL Geometric Coefficient of Variation 71.84	22.11 ng/mL Geometric Coefficient of Variation 16.80	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 365	30.16 ng/mL Geometric Coefficient of Variation 62.35	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 532	26.73 ng/mL Geometric Coefficient of Variation 44.19	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 560	26.42 ng/mL Geometric Coefficient of Variation 36.82	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 588	40.26 ng/mL Geometric Coefficient of Variation 68.00	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 616	24.69 ng/mL Geometric Coefficient of Variation 109.22	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 726	28.22 ng/mL	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 1 : Pre-dose	0.13 ng/mL Geometric Coefficient of Variation 0.00	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 1	—	0.15 ng/mL Geometric Coefficient of Variation 37.88	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 15 : Pre-dose	14.54 ng/mL Geometric Coefficient of Variation 82.48	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 210	49.04 ng/mL Geometric Coefficient of Variation 67.88	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 281	26.51 ng/mL Geometric Coefficient of Variation 73.96	23.79 ng/mL Geometric Coefficient of Variation 8.69	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 393	23.56 ng/mL Geometric Coefficient of Variation 31.29	15.36 ng/mL Geometric Coefficient of Variation 13.95	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 420	25.84 ng/mL Geometric Coefficient of Variation 42.82	21.91 ng/mL	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 448	23.53 ng/mL Geometric Coefficient of Variation 40.75	28.43 ng/mL Geometric Coefficient of Variation NA Geometric coefficient of variation is not estimable due to less number of participants.	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 476	30.87 ng/mL Geometric Coefficient of Variation 28.29	25.95 ng/mL Geometric Coefficient of Variation NA Geometric coefficient of variation is not estimable due to less number of participants.	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 504	28.24 ng/mL Geometric Coefficient of Variation 38.06	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 644	21.15 ng/mL Geometric Coefficient of Variation 39.95	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 672	30.75 ng/mL Geometric Coefficient of Variation 48.18	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 700	23.85 ng/mL Geometric Coefficient of Variation 1.63	—	—	—	—
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105 Day 728	26.28 ng/mL	—	—	—	—

SECONDARY outcome

Timeframe: Up to Day 176

Population: Assessments were planned upto Day 1009 for this OM;however no assessments were conducted after Day 176 due to early termination.Serum concentrations of BIIB105 were not estimable for Integrated Parts 1 \& 2.Data collected for serum PK concentrations for Parts 1 \& 2 are reported in OM #3 and #20(post-hoc)respectively.Treatment groups for integrated analysis of Parts 1 \& 2 were planned for Early-start BIIB105 120 mg \& Placebo/Delayed-start BIIB105,\& results are reported for these treatment groups.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=48 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=17 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Integrated Part 1 and Part 2: Serum Concentration of BIIB105	NA ng/mL Geometric Coefficient of Variation NA Data were not estimable due to values being below the lower limit of quantification	NA ng/mL Geometric Coefficient of Variation NA Data were not estimable due to values being below the lower limit of quantification	—	—	—

SECONDARY outcome

Timeframe: Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449, 477, 505, 533, 561, 589, 617, 645, 673, 701

Population: Integrated Parts 1 and 2=Part 1 PD population. Number analyzed indicates the number of participants evaluable for the OM at the specified timepoint. The treatment groups for the integrated analysis of Part 1 and Part 2 were planned for Early-start BIIB105 120 mg and Placebo/Delayed-start BIIB105, and results are reported for these treatment groups.

Plasma NfL ratio to baseline was reported in terms of geometric mean ratio.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=47 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=19 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 85	0.99 ratio Geometric Coefficient of Variation 19.62	1.00 ratio Geometric Coefficient of Variation 18.00	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 113	1.01 ratio Geometric Coefficient of Variation 21.77	1.06 ratio Geometric Coefficient of Variation 19.95	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 505	0.77 ratio Geometric Coefficient of Variation 25.18	0.88 ratio Geometric Coefficient of Variation 46.94	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 533	0.78 ratio Geometric Coefficient of Variation 14.58	1.15 ratio Geometric Coefficient of Variation 32.24	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 29	1.15 ratio Geometric Coefficient of Variation 72.72	1.03 ratio Geometric Coefficient of Variation 22.35	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 57	1.03 ratio Geometric Coefficient of Variation 21.7	1.11 ratio Geometric Coefficient of Variation 18.9	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 141	1.03 ratio Geometric Coefficient of Variation 41.35	1.10 ratio Geometric Coefficient of Variation 20.84	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 169	1.06 ratio Geometric Coefficient of Variation 24.92	1.06 ratio Geometric Coefficient of Variation 20.33	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 197	1.08 ratio Geometric Coefficient of Variation 28.28	1.08 ratio Geometric Coefficient of Variation 23.6	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 225	1.12 ratio Geometric Coefficient of Variation 38.42	1.12 ratio Geometric Coefficient of Variation 31.12	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 253	1.15 ratio Geometric Coefficient of Variation 28.4	1.06 ratio Geometric Coefficient of Variation 27.71	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 281	1.14 ratio Geometric Coefficient of Variation 26.57	1.18 ratio Geometric Coefficient of Variation 21.26	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 309	1.07 ratio Geometric Coefficient of Variation 31.81	1.09 ratio Geometric Coefficient of Variation 24.46	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 337	1.05 ratio Geometric Coefficient of Variation 38.67	1.18 ratio Geometric Coefficient of Variation 23.3	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 365	0.99 ratio Geometric Coefficient of Variation 32.42	1.20 ratio Geometric Coefficient of Variation 29.59	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 393	0.95 ratio Geometric Coefficient of Variation 48.05	1.26 ratio Geometric Coefficient of Variation 24.88	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 421	0.92 ratio Geometric Coefficient of Variation 36.61	1.21 ratio Geometric Coefficient of Variation 58.82	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 449	0.82 ratio Geometric Coefficient of Variation 28.9	1.06 ratio Geometric Coefficient of Variation 32.94	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 477	0.85 ratio Geometric Coefficient of Variation 23.15	0.92 ratio Geometric Coefficient of Variation 32.52	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 561	0.65 ratio Geometric Coefficient of Variation 14.63	—	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 589	0.77 ratio Geometric Coefficient of Variation 39.28	0.90 ratio Geometric Coefficient of Variation 23.38	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 617	0.80 ratio Geometric Coefficient of Variation 38.48	0.70 ratio	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 645	0.76 ratio Geometric Coefficient of Variation 52.68	—	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 673	0.66 ratio Geometric Coefficient of Variation 30.22	—	—	—	—
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline Day 701	0.54 ratio	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Day 281

Population: Integrated data for Part 1 and Part 2 was analyzed based on the clinical function population defined for Part 1. The Part 1 clinical function population included participants from the FAS population who have at least 1 postdose measurement in Part 1. The treatment groups for the integrated analysis of Part 1 and Part 2 were planned for Early-start BIIB105 120 mg and Placebo/Delayed-start BIIB105, and results are reported for these treatment groups.

Vital capacity was measured by means of the slow vital capacity (SVC) test using a facemask with the participant sitting upright. SVC was determined by performing at least 3 trials. If the difference between the two highest values of the three trials was ≥10%, then up to 5 trials were performed. The highest percent predicted SVC value at each visit was used for the analysis. Here, baseline is defined as Part 1 day 1 value prior to the study drug. As specified in SAP, change from baseline at Week 40 (Day 281) in least square means and corresponding standard errors was summarized using the analysis of covariance (ANCOVA) model. Negative change from baseline indicates decrease in lung function.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=48 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=19 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Integrated Part 1 and Part 2: Change From Baseline in Percent Predicted Slow Vital Capacity (SVC)	-14.49 percent predicted Standard Error 4.093	-14.41 percent predicted Standard Error 7.133	—	—	—

SECONDARY outcome

Timeframe: Baseline, Day 281

The ALSFRS-R is a questionnaire that measured degree of impairment in 4 functional domains: respiratory function, bulbar function, gross motor skills, and fine motor skills. Each domain consists of 3 items, each scored from 0 to 4, with higher scores representing better function. Each domain score can have maximum score of 12 calculated as the sum of scores of 3 items for that domain and the total possible score for ALSFRS-R is 48. The total score is the sum of the 4 functional domain scores or all individual item scores if no missing item scores are present. Here, baseline is defined as Part 1 day 1 value prior to the study drug Negative change from baseline indicates disease progression. As specified in SAP change from baseline at Week 40 (Day 281) in least square means and corresponding standard errors was summarized using the ANCOVA model.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=48 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=19 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Integrated Part 1 and Part 2: Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score	-8.46 score on a scale Standard Error 1.105	-8.26 score on a scale Standard Error 1.819	—	—	—

SECONDARY outcome

Timeframe: Baseline, Day 281

Quantitative muscle strength was evaluated using HHD, which tested the isometric strength of multiple muscles using standard participant positioning. Approximately 8 muscle groups were examined (per each side) in both upper and lower extremities. The muscle strength values were normalized to Z scores as (post-baseline measurements -mean)/SD and averaged to provide HHD overall megascore. The overall megascore was created by averaging Z scores, if no more than 14 (≤ 14) measures are missing. A Z-score (also called a standard score) is a way to describe how far and in what direction a data point is from the mean of the dataset (in this case, positive values indicate strength and negative values indicate weakness). A Z-score of 0 indicates the population mean, and a positive score indicates muscle strength. A negative change from baseline indicated decreased muscle strength.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=48 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=19 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Integrated Part 1 and Part 2: Change From Baseline in Muscle Strength as Measured by Handheld Dynamometry (HHD) Megascore	-0.407 z-score Standard Deviation 0.3918	-0.439 z-score Standard Deviation 0.4406	—	—	—

SECONDARY outcome

Timeframe: Baseline up to Day 1184

Population: Integrated data for Part 1 and Part 2 was analyzed based on the FAS population defined for Part 1. Part 1 FAS population included all randomized participants who received at least 1 dose of study treatment in Part 1 and 2. The treatment groups for the integrated analysis of Part 1 and Part 2 were planned for Early-start BIIB105 120 mg and Placebo/Delayed-start BIIB105, and results are reported for these treatment groups.

Time to death or permanent ventilation is defined as the time from first dose to death or permanent ventilation ( ≥ 22 hours of mechanical ventilation \[invasive or noninvasive\] per day for ≥ 21 consecutive days), whichever comes first. Participants who did not meet the endpoint definition were censored on the date of participant's last contact in Part 1 or Part 2. Time to death or permanent ventilation data was summarized using Kaplan-Meier curves based on randomization in Part 1.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=48 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=19 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Integrated Part 1 and Part 2: Time to Death or Permanent Ventilation	NA weeks Interval 72.7 to Median and 95% confidence interval (CI) were not estimable due to low number events of permanent ventilation or death.	NA weeks Median and 95% confidence interval (CI) were not estimable due to low number events of permanent ventilation or death.	—	—	—

SECONDARY outcome

Timeframe: Baseline up to Day 1184

Time to death was defined as the time from first dose to death.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=48 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=19 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Integrated Parts 1 and 2: Time to Death	NA weeks Median and 95% CI were not estimable due to low number of events of death.	NA weeks Median and 95% CI were not estimable due to low number of events of death.	—	—	—

SECONDARY outcome

Timeframe: Up to Day 1184

Population: As per the changes to the protocol-specified analyses mentioned in the SAP, time to death, incorporating post-study withdrawal or study completion vital status data was not performed as post-study withdrawal vital status data was not collected at the time of this analysis. The treatment groups for the integrated analysis of Part 1 and Part 2 were planned for Early-start BIIB105 120 mg and Placebo/Delayed-start BIIB105, and results are reported for these treatment groups.

Outcome measures

Outcome data not reported

POST_HOC outcome

Timeframe: Days 1, 169, 337, 505 and 673

Population: The PK analysis population is defined as all randomized participants who received at least 1 dose of study treatment and have at least 1 postdose serum and/or CSF BIIB105 measurement. 'Number analyzed' indicates the number of participants evaluable at the specified time point.

Outcome measures

Outcome measures
Measure	Part 1: Pooled Placebo 1+2 n=19 Participants Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=51 Participants Participants with ALS received 3 loading doses of BIIB105 5 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received 3 loading doses of BIIB105 120 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.
Part 2: Serum Concentration of BIIB105 Day 1	0.50 ng/mL Geometric Coefficient of Variation 0.00	1.47 ng/mL Geometric Coefficient of Variation 139.00	—	—	—
Part 2: Serum Concentration of BIIB105 Day 169	1.25 ng/mL Geometric Coefficient of Variation 186.75	3.50 ng/mL Geometric Coefficient of Variation 151.48	—	—	—
Part 2: Serum Concentration of BIIB105 Day 337	2.46 ng/mL Geometric Coefficient of Variation 333.20	2.50 ng/mL Geometric Coefficient of Variation 95.95	—	—	—
Part 2: Serum Concentration of BIIB105 Day 505	3.53 ng/mL Geometric Coefficient of Variation 340.11	8.54 ng/mL Geometric Coefficient of Variation 0.00	—	—	—
Part 2: Serum Concentration of BIIB105 Day 673	18.89 ng/mL Geometric Coefficient of Variation 164.41	—	—	—	—

Adverse Events

Part 1: Pooled Placebo 1+2

Serious events: 5 serious events

Other events: 27 other events

Deaths: 0 deaths

Part 1: Cohort A: BIIB105 5 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part 1: Cohort B: BIIB105 20 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part 1: Cohorts C1+C2: BIIB105 60 mg

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Part 1: Cohorts D1 + D2: BIIB105 120 mg

Serious events: 7 serious events

Other events: 47 other events

Deaths: 0 deaths

Part 2: BIIB105 60 mg

Serious events: 7 serious events

Other events: 19 other events

Deaths: 4 deaths

Part 2: BIIB105 120 mg

Serious events: 14 serious events

Other events: 45 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Part 1: Pooled Placebo 1+2 n=28 participants at risk Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=6 participants at risk Participants with ALS received 3 loading doses of BIIB105 5mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg n=6 participants at risk Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg n=11 participants at risk Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg n=48 participants at risk Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received BIIB105 120 mg, IT, as 3 loading doses administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 2: BIIB105 60 mg n=19 participants at risk Participants from cohorts A-C2, who received 5, 20 and 60 mg doses of BIIB105 and placebo in Part 1 and completed Week 25 (Day 175) visit in Part 1 received BIIB105 60 mg in Part 2.	Part 2: BIIB105 120 mg n=51 participants at risk Participants from Cohorts D1 and D2 who received 120 mg dose of BIIB105 and placebo in Part 1 and completed Week 25 (Day 176) visit in Part 1 received BIIB105 120 mg in Part 2.
Gastrointestinal disorders Dysphagia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Food poisoning	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Ileus	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Covid-19	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Pneumonia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Pneumonia aspiration	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Pulmonary sepsis	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Sepsis	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Urosepsis	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Craniofacial fracture	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Fall	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Jaw fracture	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Subdural haematoma	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Tendon rupture	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Metabolism and nutrition disorders Dehydration	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Metabolism and nutrition disorders Malnutrition	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Seronegative arthritis	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Amyotrophic lateral sclerosis	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Balance disorder	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Cerebral venous sinus thrombosis	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Radiculopathy	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Toxic encephalopathy	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Respiratory, thoracic and mediastinal disorders Chronic respiratory failure	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.9% 3/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.

Other adverse events

Other adverse events
Measure	Part 1: Pooled Placebo 1+2 n=28 participants at risk Participants with ALS and polyQ-ALS from Cohorts A, B, C1 and C2 received 3 loading doses of BIIB105-matched placebo, administered every 2 weeks (on Days 1, 15 and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks. Participants with ALS and polyQ-ALS from Cohorts D1 and D2 received 3 loading doses of BIIB105- matched placebo administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 1: Cohort A: BIIB105 5 mg n=6 participants at risk Participants with ALS received 3 loading doses of BIIB105 5mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohort B: BIIB105 20 mg n=6 participants at risk Participants with ALS received 3 loading doses of BIIB105 20 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts C1+C2: BIIB105 60 mg n=11 participants at risk Participants with ALS (Cohort C1) and polyQ-ALS (Cohort C2) received 3 loading doses of BIIB105 60 mg, IT, administered every 2 weeks (on Days 1, 15, and 29), followed by 2 maintenance doses administered once every 4 weeks (on Days 57 and 85), for a total of 5 doses over approximately 13 weeks.	Part 1: Cohorts D1 + D2: BIIB105 120 mg n=48 participants at risk Participants with ALS (Cohort D1) and polyQ-ALS (Cohort D2) received BIIB105 120 mg, IT, as 3 loading doses administered every 2 weeks (on Days 1, 15, and 29), followed by 5 maintenance doses administered once every 4 weeks (on Days 57, 85, 113, 141, and 169), for a total of 8 doses over approximately 25 weeks.	Part 2: BIIB105 60 mg n=19 participants at risk Participants from cohorts A-C2, who received 5, 20 and 60 mg doses of BIIB105 and placebo in Part 1 and completed Week 25 (Day 175) visit in Part 1 received BIIB105 60 mg in Part 2.	Part 2: BIIB105 120 mg n=51 participants at risk Participants from Cohorts D1 and D2 who received 120 mg dose of BIIB105 and placebo in Part 1 and completed Week 25 (Day 176) visit in Part 1 received BIIB105 120 mg in Part 2.
Investigations Alanine aminotransferase increased	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Investigations Aspartate aminotransferase increased	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Investigations Blood uric acid increased	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Investigations Csf white blood cell count increased	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	12.5% 6/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	15.8% 3/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	13.7% 7/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Investigations Breath sounds abnormal	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Investigations Csf protein increased	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	22.9% 11/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	21.1% 4/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	13.7% 7/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Cardiac disorders Tachycardia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Ear and labyrinth disorders Ear pain	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Ear and labyrinth disorders Hypoacusis	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Ear and labyrinth disorders Tinnitus	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Ear and labyrinth disorders Vertigo positional	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Eye disorders Conjunctival haemorrhage	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Abdominal distension	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Constipation	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	31.6% 6/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	13.7% 7/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Diarrhoea	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	14.6% 7/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	21.1% 4/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	7.8% 4/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Dysphagia	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Food poisoning	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Gastritis	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Haematemesis	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Hiatus hernia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Mouth ulceration	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Nausea	10.7% 3/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	33.3% 2/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	27.3% 3/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.4% 5/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	21.1% 4/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Oesophagitis	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Oral dysaesthesia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Salivary hypersecretion	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Gastrointestinal disorders Vomiting	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	6.2% 3/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
General disorders Asthenia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.4% 5/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	7.8% 4/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
General disorders Chest pain	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
General disorders Chills	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	8.3% 4/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
General disorders Fatigue	10.7% 3/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	45.5% 5/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 8/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	15.8% 3/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	13.7% 7/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
General disorders Medical device site burn	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
General disorders Oedema	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
General disorders Oedema peripheral	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
General disorders Pain	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
General disorders Peripheral swelling	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	6.2% 3/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
General disorders Pyrexia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.8% 5/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
General disorders Swelling face	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
General disorders Vaccination site pain	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Immune system disorders Seasonal allergy	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Covid-19	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	8.3% 4/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	21.1% 4/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	11.8% 6/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Device related infection	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Gastroenteritis viral	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Hordeolum	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Influenza	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	7.8% 4/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Nasopharyngitis	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	6.2% 3/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	11.8% 6/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Pneumonia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Sinusitis	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Stoma site infection	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Upper respiratory tract infection	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Infections and infestations Urinary tract infection	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.9% 3/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Bone contusion	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	6.2% 3/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Concussion	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Contusion	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.4% 5/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Fall	50.0% 14/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	66.7% 4/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	36.4% 4/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	37.5% 18/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	47.4% 9/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	37.3% 19/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Head injury	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Immunisation reaction	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Musculoskeletal procedural complication	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Neurological procedural complication	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Post lumbar puncture syndrome	25.0% 7/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	50.0% 3/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	54.5% 6/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	31.2% 15/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	36.8% 7/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	13.7% 7/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Post procedural contusion	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Post procedural discomfort	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Post procedural inflammation	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Post procedural swelling	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Procedural complication	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Procedural dizziness	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Procedural nausea	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	18.2% 2/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Procedural pain	53.6% 15/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	83.3% 5/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	66.7% 4/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	63.6% 7/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	52.1% 25/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	68.4% 13/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	39.2% 20/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Procedural vomiting	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Rib fracture	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Shoulder fracture	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	27.3% 3/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.9% 3/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	18.2% 2/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.9% 3/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Stoma site discharge	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Injury, poisoning and procedural complications Stoma site pain	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Investigations Gamma-glutamyltransferase increased	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Investigations Hepatic enzyme increased	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Investigations Weight decreased	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	21.1% 4/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	11.8% 6/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Metabolism and nutrition disorders Dehydration	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Arthralgia	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	33.3% 2/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	50.0% 3/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	36.4% 4/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	12.5% 6/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	15.8% 3/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	21.6% 11/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Back pain	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	33.3% 2/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	27.3% 3/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	25.0% 12/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Mobility decreased	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Muscle spasms	21.4% 6/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	33.3% 2/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	36.4% 4/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	6.2% 3/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Muscle tightness	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Muscular weakness	10.7% 3/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	18.8% 9/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	15.8% 3/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	13.7% 7/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	18.2% 2/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.8% 5/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Myalgia	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	18.2% 2/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	14.6% 7/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	13.7% 7/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	18.2% 2/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	15.8% 3/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Musculoskeletal and connective tissue disorders Pain in extremity	25.0% 7/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	18.2% 2/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	22.9% 11/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	21.1% 4/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	13.7% 7/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Balance disorder	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	12.5% 6/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.9% 3/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Brain fog	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Clonus	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Cluster headache	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Cognitive disorder	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Dizziness	10.7% 3/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	18.2% 2/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 8/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.8% 5/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Dysgeusia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Head discomfort	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Headache	42.9% 12/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	50.0% 3/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	66.7% 4/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	45.5% 5/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	58.3% 28/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	26.3% 5/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	37.3% 19/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Hemihypoaesthesia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Hypoaesthesia	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Loss of consciousness	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Menstrual headache	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Muscle contractions involuntary	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Neuropathy peripheral	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Paraesthesia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	8.3% 4/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Parosmia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Pleocytosis	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	12.5% 6/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	15.8% 3/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	7.8% 4/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Post-traumatic headache	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Presyncope	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Radicular pain	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Sciatica	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Speech disorder	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Nervous system disorders Syncope	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Product Issues Device dislocation	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Psychiatric disorders Affect lability	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Psychiatric disorders Anxiety	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	8.3% 4/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Psychiatric disorders Confusional state	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Psychiatric disorders Depression	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Psychiatric disorders Insomnia	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Psychiatric disorders Sleep disorder	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Psychiatric disorders Suicidal ideation	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	3.9% 2/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Renal and urinary disorders Pollakiuria	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	15.8% 3/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Renal and urinary disorders Urinary retention	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.8% 5/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Reproductive system and breast disorders Breast pain	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Respiratory, thoracic and mediastinal disorders Cough	14.3% 4/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	7.8% 4/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.9% 3/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Respiratory, thoracic and mediastinal disorders Dyspnoea at rest	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Respiratory, thoracic and mediastinal disorders Laryngospasm	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	10.5% 2/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.9% 3/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Skin and subcutaneous tissue disorders Erythema	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Skin and subcutaneous tissue disorders Hyperhidrosis	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Skin and subcutaneous tissue disorders Nodular rash	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Skin and subcutaneous tissue disorders Pruritus	7.1% 2/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	4.2% 2/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Skin and subcutaneous tissue disorders Rash	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.1% 1/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	11.8% 6/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	9.1% 1/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Vascular disorders Deep vein thrombosis	3.6% 1/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Vascular disorders Flushing	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	16.7% 1/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.
Vascular disorders Hypertension	0.00% 0/28 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/6 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/11 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	0.00% 0/48 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	5.3% 1/19 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.	2.0% 1/51 • From first dose of the study drug up to end of follow up period in Part 1 (up to Day 260) and Part 2 (up to Day 1184) The Part 1 safety analysis population included all randomized participants who received at least 1 dose of study treatment in Part 1. The Part 2 safety analysis population included all participants who received at least 1 dose of study treatment in Part 2.

Additional Information

US Biogen Clinical Trial Center

Biogen

Phone: 866-633-4636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER