Trial Outcomes & Findings for Efficacy and Safety Study of Mepolizumab in Subjects With Severe Hypereosinophilic Syndrome (HES) (NCT NCT02836496)

NCT ID: NCT02836496

Last Updated: 2020-02-21

Results Overview

Percentage of participants who experienced \>=1 HES flare during the 32-Week treatment period or who withdrew from the study has been presented. A HES flare is defined as a HES related clinical manifestation based on a physician-documented change in clinical signs or symptoms which resulted in need for an increase in the maintenance Oral Corticosteroid (OCS) dose by at least 10 mg per day for 5 days or an increase in or addition of any cytotoxic or immunosuppressive HES therapy. HES flare is also defined as receipt of two or more courses of blinded active OCS during the treatment period. Intent-to-treat (ITT) Population comprises of all randomized participants. This population was based on the treatment to which the participants were randomized. Any participant who received a treatment randomization number were considered to be randomized.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 108 participants
• Primary outcome timeframe: Up to Week 32
• Results posted on: 2020-02-21

Participant Flow

This 32-week, randomized, double-blind, placebo-controlled study assessed the efficacy and safety of mepolizumab 300 milligrams (mg) subcutaneous (SC) every 4 weeks compared with placebo in adolescent and adult participants with severe hypereosinophilic syndrome (HES) receiving standard of care (SoC) therapy.

A total of 108 participants were enrolled in the study and randomized. The study was conducted in 13 countries.

Participant milestones

Measure	Placebo Participants were randomized to receive matching placebo SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.	Mepolizumab 300 mg SC Participants were randomized to receive 300 mg mepolizumab SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.
Overall Study STARTED	54	54
Overall Study COMPLETED	52	52
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Measure	Placebo Participants were randomized to receive matching placebo SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.	Mepolizumab 300 mg SC Participants were randomized to receive 300 mg mepolizumab SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.
Overall Study Adverse Event	2	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Efficacy and Safety Study of Mepolizumab in Subjects With Severe Hypereosinophilic Syndrome (HES)

Baseline characteristics by cohort

Measure	Placebo n=54 Participants Participants were randomized to receive matching placebo SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.	Mepolizumab 300 mg SC n=54 Participants Participants were randomized to receive 300 mg mepolizumab SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.	Total n=108 Participants Total of all reporting groups
Age, Continuous	45.4 Years STANDARD_DEVIATION 18.25 • n=5 Participants	46.6 Years STANDARD_DEVIATION 12.99 • n=7 Participants	46.0 Years STANDARD_DEVIATION 15.78 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	30 Participants n=7 Participants	57 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	24 Participants n=7 Participants	51 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian-Central/South Asian Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian-East Asian Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian-South East Asian Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White-Arabic/North African Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White-White/Caucasian/European Heritage	47 Participants n=5 Participants	52 Participants n=7 Participants	99 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 32

Population: ITT Population.

Percentage of participants who experienced >=1 HES flare during the 32-Week treatment period or who withdrew from the study has been presented. A HES flare is defined as a HES related clinical manifestation based on a physician-documented change in clinical signs or symptoms which resulted in need for an increase in the maintenance Oral Corticosteroid (OCS) dose by at least 10 mg per day for 5 days or an increase in or addition of any cytotoxic or immunosuppressive HES therapy. HES flare is also defined as receipt of two or more courses of blinded active OCS during the treatment period. Intent-to-treat (ITT) Population comprises of all randomized participants. This population was based on the treatment to which the participants were randomized. Any participant who received a treatment randomization number were considered to be randomized.

Outcome measures

Measure	Placebo n=54 Participants Participants were randomized to receive matching placebo SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.	Mepolizumab 300 mg SC n=54 Participants Participants were randomized to receive 300 mg mepolizumab SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.
Percentage of Participants Who Experienced an HES Flare or Who Withdrew From the Study During the 32-Week Study Treatment Period	56 Percentage of participants	28 Percentage of participants

SECONDARY outcome

Timeframe: Week 20 to Week 32

Population: ITT Population.

HES flare during Week 20 through Week 32 was defined as a HES flare starting or ongoing on or after the date of the Week 20 visit up to and including the date of the Week 32 visit. Percentage of participants who experienced >=1 HES flare during Week 20 through Week 32 or who withdrew from the study has been presented.

Outcome measures

Measure	Placebo n=54 Participants Participants were randomized to receive matching placebo SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.	Mepolizumab 300 mg SC n=54 Participants Participants were randomized to receive 300 mg mepolizumab SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.
Percentage of Participants Who Experienced a HES Flare or Who Withdrew From the Study During Week 20 Through Week 32	35 Percentage of participants	17 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28 and 32

Population: ITT Population.

The time to first HES flare was calculated as (onset date of first HES flare minus date of first dose of study treatment) plus 1. Probability of first flare (by week 4, 8, 12, 16, 20, 24, 28, and 32) and corresponding 95% CI have been presented, calculated using the Kaplan-Meier method.

Outcome measures

Measure	Placebo n=54 Participants Participants were randomized to receive matching placebo SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.	Mepolizumab 300 mg SC n=54 Participants Participants were randomized to receive 300 mg mepolizumab SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.
Time to First HES Flare Flares by Week 8	14.9 Probability expressed as percentage Interval 7.7 to 27.5	7.4 Probability expressed as percentage Interval 2.8 to 18.5
Time to First HES Flare Flares by Week 12	26.2 Probability expressed as percentage Interval 16.4 to 40.2	9.3 Probability expressed as percentage Interval 4.0 to 20.8
Time to First HES Flare Flares by Week 16	33.8 Probability expressed as percentage Interval 22.8 to 48.1	13.0 Probability expressed as percentage Interval 6.4 to 25.3
Time to First HES Flare Flares by Week 20	41.3 Probability expressed as percentage Interval 29.5 to 55.7	13.0 Probability expressed as percentage Interval 6.4 to 25.3
Time to First HES Flare Flares by Week 24	48.9 Probability expressed as percentage Interval 36.5 to 63.0	14.8 Probability expressed as percentage Interval 7.7 to 27.4
Time to First HES Flare Flares by Week 28	50.8 Probability expressed as percentage Interval 38.3 to 64.8	20.5 Probability expressed as percentage Interval 11.9 to 34.0
Time to First HES Flare Flares by Week 4	7.4 Probability expressed as percentage Interval 2.8 to 18.5	5.6 Probability expressed as percentage Interval 1.8 to 16.2
Time to First HES Flare Flares by Week 32	52.7 Probability expressed as percentage Interval 40.1 to 66.5	26.3 Probability expressed as percentage Interval 16.5 to 40.3

SECONDARY outcome

Timeframe: Up to Week 32

Population: ITT Population.

The rate of HES flares for each participant was calculated as the number of observed HES flares divided by the time (expressed in years) between randomization and either the week 32 visit date if available, or the study withdrawal date. Negative binomial generalized linear model including Baseline OCS dose, region, treatment and observed time (offset variable). Wilcoxon test stratified by Baseline OCS (0-<=20mg/day, >20mg/day prednisone or equivalent) and region. Adjusted mean and 95% CI rate/year has been presented.

Outcome measures

Measure	Placebo n=54 Participants Participants were randomized to receive matching placebo SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.	Mepolizumab 300 mg SC n=54 Participants Participants were randomized to receive 300 mg mepolizumab SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.
Number of HES Flares Per Participant Per Year	1.46 Flares per participant per year Interval 1.05 to 2.02	0.50 Flares per participant per year Interval 0.3 to 0.84

SECONDARY outcome

Timeframe: Baseline (Week 0) and at Week 32

Population: ITT Population.

The change from Baseline in fatigue severity (worst level of fatigue during past 24 hours) at Week 32 was calculated using the mean of the 7 daily assessments of BFI item 3 up to and including the date of the Week 32 visit as the Week 32 assessment, and the mean of the 7 daily assessments of BFI item 3 up to but not including the date of first dose of study treatment as the Baseline assessment. Wilcoxon Rank Sum test stratified by Baseline fatigue severity ("severe" defined as BFI item 3>=7 and "not severe" defined as BFI item 3<7), Baseline OCS (0-<=20mg/day and >20mg/day prednisone or equivalent) and region. Participants with missing change from Baseline at Week 32 were included in the worst category (>=4 point increase).

Outcome measures

Measure	Placebo n=54 Participants Participants were randomized to receive matching placebo SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.	Mepolizumab 300 mg SC n=54 Participants Participants were randomized to receive 300 mg mepolizumab SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.
Number of Participants With Change From Baseline in Fatigue Severity Based on Brief Fatigue Inventory (BFI) in Item 3 (Worst Level of Fatigue During Past 24 Hours) at Week 32 by Category 3 point increase (>=2.5 to <3.5)	4 Participants	0 Participants
Number of Participants With Change From Baseline in Fatigue Severity Based on Brief Fatigue Inventory (BFI) in Item 3 (Worst Level of Fatigue During Past 24 Hours) at Week 32 by Category 2 point increase (>=1.5 to <2.5)	4 Participants	5 Participants
Number of Participants With Change From Baseline in Fatigue Severity Based on Brief Fatigue Inventory (BFI) in Item 3 (Worst Level of Fatigue During Past 24 Hours) at Week 32 by Category No change (>-0.5 to <0.5)	14 Participants	9 Participants
Number of Participants With Change From Baseline in Fatigue Severity Based on Brief Fatigue Inventory (BFI) in Item 3 (Worst Level of Fatigue During Past 24 Hours) at Week 32 by Category >=4 point increase (>=3.5)	7 Participants	5 Participants
Number of Participants With Change From Baseline in Fatigue Severity Based on Brief Fatigue Inventory (BFI) in Item 3 (Worst Level of Fatigue During Past 24 Hours) at Week 32 by Category 1 point increase (>=0.5 to <1.5)	9 Participants	6 Participants
Number of Participants With Change From Baseline in Fatigue Severity Based on Brief Fatigue Inventory (BFI) in Item 3 (Worst Level of Fatigue During Past 24 Hours) at Week 32 by Category 1 point reduction (>-1.5 to <=-0.5)	5 Participants	11 Participants
Number of Participants With Change From Baseline in Fatigue Severity Based on Brief Fatigue Inventory (BFI) in Item 3 (Worst Level of Fatigue During Past 24 Hours) at Week 32 by Category 2 point reduction (>-2.5 to <=-1.5)	3 Participants	7 Participants
Number of Participants With Change From Baseline in Fatigue Severity Based on Brief Fatigue Inventory (BFI) in Item 3 (Worst Level of Fatigue During Past 24 Hours) at Week 32 by Category 3 point reduction (>-3.5 to <=-2.5)	5 Participants	2 Participants
Number of Participants With Change From Baseline in Fatigue Severity Based on Brief Fatigue Inventory (BFI) in Item 3 (Worst Level of Fatigue During Past 24 Hours) at Week 32 by Category >=4 point reduction (<=-3.5)	3 Participants	9 Participants

Adverse Events

Placebo

Serious events: 9 serious events

Other events: 43 other events

Deaths: 0 deaths

Mepolizumab 300 mg SC

Serious events: 10 serious events

Other events: 41 other events

Deaths: 1 deaths

Serious adverse events

Measure	Placebo n=54 participants at risk Participants were randomized to receive matching placebo SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.	Mepolizumab 300 mg SC n=54 participants at risk Participants were randomized to receive 300 mg mepolizumab SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.
Infections and infestations Bronchitis	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Bursitis infective	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Diverticulitis	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Erysipelas	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Gastroenteritis	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Liver abscess	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Pneumonia	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Septic shock	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Tooth infection	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal pain	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal pain upper	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Gastrointestinal disorders Faecaloma	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Gastrointestinal disorders Vomiting	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) T-cell lymphoma	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Blood and lymphatic system disorders Hypereosinophilic syndrome	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Cardiac disorders Arrhythmia	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Cardiac disorders Restrictive cardiomyopathy	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Injury, poisoning and procedural complications Contusion	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Vascular disorders Hypertension	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Vascular disorders Peripheral artery occlusion	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Immune system disorders Anaphylactic reaction	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.

Other adverse events

Measure	Placebo n=54 participants at risk Participants were randomized to receive matching placebo SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.	Mepolizumab 300 mg SC n=54 participants at risk Participants were randomized to receive 300 mg mepolizumab SC every 4 weeks during the 32-Week treatment period while continuing their HES therapy. The final dose was administered at Week 28 with the completion of study treatment period achieved in the next 4-weekly visit.
Infections and infestations Bronchitis	18.5% 10/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	13.0% 7/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Nasopharyngitis	13.0% 7/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	13.0% 7/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Rhinitis	11.1% 6/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	9.3% 5/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Upper respiratory tract infection	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	14.8% 8/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Sinusitis	7.4% 4/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Urinary tract infection	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	9.3% 5/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Influenza	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Oral herpes	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Cystitis	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Gastroenteritis	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Arthritis infective	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Gastroenteritis viral	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Onychomycosis	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Infections and infestations Respiratory tract infection	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Asthma	9.3% 5/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Nasal obstruction	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	7.4% 4/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	7.4% 4/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Gastrointestinal disorders Diarrhoea	13.0% 7/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	9.3% 5/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Gastrointestinal disorders Vomiting	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Gastrointestinal disorders Nausea	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Gastrointestinal disorders Constipation	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal pain	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal pain upper	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Gastrointestinal disorders Stomatitis	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Gastrointestinal disorders Toothache	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
General disorders Fatigue	9.3% 5/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
General disorders Pyrexia	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	7.4% 4/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
General disorders Asthenia	9.3% 5/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
General disorders Influenza like illness	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
General disorders Injection site reaction	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
General disorders Peripheral swelling	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
General disorders Malaise	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	7.4% 4/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	7.4% 4/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	11.1% 6/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Myalgia	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	7.4% 4/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Back pain	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Nervous system disorders Headache	13.0% 7/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	13.0% 7/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Nervous system disorders Dizziness	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	7.4% 4/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Nervous system disorders Hypoaesthesia	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Nervous system disorders Paraesthesia	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Nervous system disorders Presyncope	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Nervous system disorders Somnolence	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Pruritus	13.0% 7/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	7.4% 4/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Urticaria	9.3% 5/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	7.4% 4/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Rash	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Eczema	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Erythema	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Injury, poisoning and procedural complications Contusion	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Reproductive system and breast disorders Erectile dysfunction	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Metabolism and nutrition disorders Decreased appetite	5.6% 3/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Vascular disorders Hypertension	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	1.9% 1/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Cardiac disorders Palpitations	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.
Ear and labyrinth disorders Tinnitus	0.00% 0/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.	3.7% 2/54 • Non-serious adverse events (non-SAEs) from start of study treatment until 28 days after last dose (Up to 32 weeks) are reported. Serious adverse events (SAEs) were collected from the day of randomization (Week 0) up to end of study (Up to Week 40). Non-SAEs and SAEs were collected for Safety Population. The Safety Population comprises of all participants who were randomized and who received at least one dose of study treatment.

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