Trial Outcomes & Findings for Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease (NCT NCT01753401)

NCT ID: NCT01753401

Last Updated: 2020-02-27

Results Overview

Participants are counted as responders based on two SLE indices: the Systemic Lupus Erythematosus Disease Activity Index amended by the SELENA group (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) Index. * decrease in SELENA-SLEDAI score from 4 to 0 for the arthritis descriptor (highest possible score is 4) and no worsening in other organ systems based on BILAG OR * decrease in SELENA-SLEDAI score from 2 to 0 for rash (highest possible score is 2) and no worsening in other organ systems based on BILAG The BILAG is a transitional index that captures changing severity of clinical manifestations. It has an ordinal scale scoring system by design that produces an overview of disease activity across eight systems. The individual system scores were not intended to be summated into a global score.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 38 participants
• Primary outcome timeframe: within 4 weeks
• Results posted on: 2020-02-27

Participant Flow

38 enrolled participants were randomized 2:1:2:1 into four treatment groups, to receive Acthar 0.5 mL daily: Placebo 0.5 mL daily: Acthar 1 mL every other day: Placebo 1 mL every other day, during the double-blind period, along with their stable dose of steroids.

All participants were to receive their stable steroid regimen in addition to the study drug throughout the double-blind period (Period 1). If they completed Period 1, they were invited to participate in an open label period (Period 2). Those who received Placebo went into Placebo/Acthar, and those who received Acthar went into Acthar/Acthar.

Participant milestones

Measure	Placebo Participants receive their randomized regimen of placebo during the double-blind period	Acthar Participants receive their randomized regimen of Acthar during the double-blind period	Placebo/Acthar Participants who receive Placebo in Part 1, but Acthar in Part 2	Acthar/Acthar Participants who receive Acthar in both Parts 1 and 2
Double-blind Period (8 Weeks) STARTED	12	26	0	0
Double-blind Period (8 Weeks) Modified Intent to Treat (mITT)	11	25	0	0
Double-blind Period (8 Weeks) COMPLETED	11	22	0	0
Double-blind Period (8 Weeks) NOT COMPLETED	1	4	0	0
Open Label Period (44 Weeks) STARTED	0	0	11	22
Open Label Period (44 Weeks) mITT	0	0	11	22
Open Label Period (44 Weeks) Safety Analysis Set	0	0	11	22
Open Label Period (44 Weeks) COMPLETED	0	0	7	13
Open Label Period (44 Weeks) NOT COMPLETED	0	0	4	9

Reasons for withdrawal

Measure	Placebo Participants receive their randomized regimen of placebo during the double-blind period	Acthar Participants receive their randomized regimen of Acthar during the double-blind period	Placebo/Acthar Participants who receive Placebo in Part 1, but Acthar in Part 2	Acthar/Acthar Participants who receive Acthar in both Parts 1 and 2
Double-blind Period (8 Weeks) Adverse Event	0	2	0	0
Double-blind Period (8 Weeks) Withdrawal by Subject	1	1	0	0
Double-blind Period (8 Weeks) Protocol Violation	0	1	0	0
Open Label Period (44 Weeks) Adverse Event	0	0	3	4
Open Label Period (44 Weeks) Withdrawal by Subject	0	0	0	2
Open Label Period (44 Weeks) Lack of Efficacy	0	0	1	1
Open Label Period (44 Weeks) Reason not provided	0	0	0	2

Baseline Characteristics

Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease

Baseline characteristics by cohort

Measure	Placebo n=11 Participants Participants who were randomized to receive Placebo in Period 1	Acthar n=25 Participants Participants who were randomized to receive Acthar in Period 1	Total n=36 Participants Total of all reporting groups
Age, Continuous	39 years n=5 Participants	43 years n=7 Participants	41.5 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	24 Participants n=7 Participants	34 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White or Caucasian	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	6 Participants n=5 Participants	18 Participants n=7 Participants	24 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino Ethnicity	0 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants	25 participants n=7 Participants	36 participants n=5 Participants

PRIMARY outcome

Timeframe: within 4 weeks

Population: mITT

Participants are counted as responders based on two SLE indices: the Systemic Lupus Erythematosus Disease Activity Index amended by the SELENA group (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) Index.

• decrease in SELENA-SLEDAI score from 4 to 0 for the arthritis descriptor (highest possible score is 4) and no worsening in other organ systems based on BILAG

OR

• decrease in SELENA-SLEDAI score from 2 to 0 for rash (highest possible score is 2) and no worsening in other organ systems based on BILAG

The BILAG is a transitional index that captures changing severity of clinical manifestations. It has an ordinal scale scoring system by design that produces an overview of disease activity across eight systems. The individual system scores were not intended to be summated into a global score.

Outcome measures

Measure	Placebo n=11 Participants Participants who receive Placebo in Period 1	Acthar n=25 Participants Participants who receive Acthar in Period 1
Number of Participants Who Meet the Definition of a Responder Within 4 Weeks	3 Participants	4 Participants

SECONDARY outcome

Timeframe: within 8 weeks

Population: mITT

Participants are counted as responders based on:

• decrease in SELENA-SLEDAI score from 4 to 0 for arthritis and no worsening in other organ systems based on BILAG

OR

• decrease in SELENA-SLEDAI score from 2 to 0 for rash and no worsening in other organ systems based on BILAG

Outcome measures

Measure	Placebo n=11 Participants Participants who receive Placebo in Period 1	Acthar n=25 Participants Participants who receive Acthar in Period 1
Number of Participants Who Meet the Definition of a Responder Within 8 Weeks	3 Participants	11 Participants

SECONDARY outcome

Timeframe: within 8 weeks

Population: mITT

SLEDAI was modeled on the basis of clinician global judgment. A participant's SELENA-SLEDAI total score is the sum of all marked SLE-related descriptors on a checklist developed by the SELENA Group (also referred to as hybrid SLEDAI).

The scores of the descriptors range from 0 to 8. A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity.

Rows: Week 2, Week 4, Week 6, Week 8

Outcome measures

Measure	Placebo n=11 Participants Participants who receive Placebo in Period 1	Acthar n=25 Participants Participants who receive Acthar in Period 1
Score on the SELENA-SLEDAI Within 8 Weeks Week 2	10.0 score on a scale Interval 2.0 to 12.0	8.0 score on a scale Interval 2.0 to 20.0
Score on the SELENA-SLEDAI Within 8 Weeks Week 4	9.0 score on a scale Interval 2.0 to 12.0	8.0 score on a scale Interval 4.0 to 20.0
Score on the SELENA-SLEDAI Within 8 Weeks Week 6	8.0 score on a scale Interval 2.0 to 12.0	6.0 score on a scale Interval 0.0 to 16.0
Score on the SELENA-SLEDAI Within 8 Weeks Week 8	9.0 score on a scale Interval 2.0 to 16.0	6.0 score on a scale Interval 0.0 to 13.0

SECONDARY outcome

Timeframe: within 8 weeks

Population: mITT

The BILAG is a transitional index that captures changing severity of clinical manifestations that produces an overview of disease activity across eight systems.

The 8 systems are scored on a scale from 0=not present to 4=worse, for the 4 week period before the assessment. The lowest possible score is 0, and the highest possible score is 32. A higher score means the symptoms are worse.

Rows: Baseline, Week 4, Week 8

Outcome measures

Measure	Placebo n=11 Participants Participants who receive Placebo in Period 1	Acthar n=25 Participants Participants who receive Acthar in Period 1
BILAG Total Score Within 8 Weeks at Baseline	15.4 score on a scale Standard Deviation 9.55	15.7 score on a scale Standard Deviation 5.93
BILAG Total Score Within 8 Weeks at Week 4	10.3 score on a scale Standard Deviation 7.80	9.2 score on a scale Standard Deviation 5.36
BILAG Total Score Within 8 Weeks at Week 8	13.5 score on a scale Standard Deviation 8.82	6.8 score on a scale Standard Deviation 4.31

SECONDARY outcome

Timeframe: at Baseline

Population: mITT

PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.

Outcome measures

Measure	Placebo n=11 Participants Participants who receive Placebo in Period 1	Acthar n=25 Participants Participants who receive Acthar in Period 1
Physician's Global Assessment (PGA) of Disease Severity at Baseline None	0 Participants	0 Participants
Physician's Global Assessment (PGA) of Disease Severity at Baseline Mild	1 Participants	2 Participants
Physician's Global Assessment (PGA) of Disease Severity at Baseline Moderate	8 Participants	19 Participants
Physician's Global Assessment (PGA) of Disease Severity at Baseline Severe	2 Participants	4 Participants
Physician's Global Assessment (PGA) of Disease Severity at Baseline Missing	0 Participants	0 Participants

SECONDARY outcome

Timeframe: at Week 4

Population: mITT

PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.

Outcome measures

Measure	Placebo n=11 Participants Participants who receive Placebo in Period 1	Acthar n=25 Participants Participants who receive Acthar in Period 1
Physician's Global Assessment (PGA) of Disease Severity at Week 4 None	0 Participants	1 Participants
Physician's Global Assessment (PGA) of Disease Severity at Week 4 Mild	5 Participants	9 Participants
Physician's Global Assessment (PGA) of Disease Severity at Week 4 Moderate	3 Participants	11 Participants
Physician's Global Assessment (PGA) of Disease Severity at Week 4 Severe	2 Participants	1 Participants
Physician's Global Assessment (PGA) of Disease Severity at Week 4 Missing	1 Participants	3 Participants

SECONDARY outcome

Timeframe: at Week 8

Population: mITT

PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.

Outcome measures

Measure	Placebo n=11 Participants Participants who receive Placebo in Period 1	Acthar n=25 Participants Participants who receive Acthar in Period 1
Physician's Global Assessment (PGA) of Disease Severity at Week 8 None	0 Participants	2 Participants
Physician's Global Assessment (PGA) of Disease Severity at Week 8 Mild	5 Participants	12 Participants
Physician's Global Assessment (PGA) of Disease Severity at Week 8 Moderate	3 Participants	7 Participants
Physician's Global Assessment (PGA) of Disease Severity at Week 8 Severe	3 Participants	1 Participants
Physician's Global Assessment (PGA) of Disease Severity at Week 8 Missing	0 Participants	3 Participants

SECONDARY outcome

Timeframe: at Baseline, Week 4, and Week 8 (within 8 weeks)

Population: mITT

The doctor counted the number of tender or swollen joints at Baseline, at Week 4, and at Week 8

Outcome measures

Measure	Placebo n=11 Participants Participants who receive Placebo in Period 1	Acthar n=25 Participants Participants who receive Acthar in Period 1
Number of Tender or Swollen Joints Within 8 Weeks at Baseline	6.2 Tender or Swollen Joints Standard Deviation 5.40	9.6 Tender or Swollen Joints Standard Deviation 6.90
Number of Tender or Swollen Joints Within 8 Weeks at Week 4	3.8 Tender or Swollen Joints Standard Deviation 4.34	4.5 Tender or Swollen Joints Standard Deviation 4.94
Number of Tender or Swollen Joints Within 8 Weeks at Week 8	4.0 Tender or Swollen Joints Standard Deviation 6.18	3.5 Tender or Swollen Joints Standard Deviation 5.89

SECONDARY outcome

Timeframe: at Baseline, Week 4 and Week 8 (within 8 weeks)

Population: mITT

The CLASI consists of two scores the first summarizes the activity of the disease while the second is a measure of the damage done by the disease. Activity is scored on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The CLASI score ranges from 0 to 70, with higher scores indicating more severe skin disease.

Rows: at Baseline, at Week 4, at Week 8

Outcome measures

Measure	Placebo n=11 Participants Participants who receive Placebo in Period 1	Acthar n=25 Participants Participants who receive Acthar in Period 1
Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Within 8 Weeks at Week 8	5.7 score on a scale Standard Deviation 6.87	3.7 score on a scale Standard Deviation 4.24
Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Within 8 Weeks at Baseline	6.1 score on a scale Standard Deviation 6.63	6.4 score on a scale Standard Deviation 6.33
Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Within 8 Weeks at Week 4	6.3 score on a scale Standard Deviation 4.60	4.8 score on a scale Standard Deviation 4.08

SECONDARY outcome

Timeframe: at Baseline, Week 4 and Week 8 (within 8 weeks)

Population: mITT

The Krupp FSS is a scale to rate disability-related fatigue. Respondents use a scale ranging from 1 ("completely disagree") to 7 ("completely agree") to indicate their agreement with nine statements about fatigue. A visual analogue scale is also included with the scale; respondents are asked to denote the severity of their fatigue over the past 2 weeks by placing a mark on a line extending from "no fatigue" to "fatigue as bad as could be." Higher scores on the scale are indicative of more severe fatigue.

This validated fatigue severity scale measures impact of fatigue with a 9-item questionnaire, with a 7-point Likert scale for each question. Total score ranges from 0 (best possible outcome) to 63 (worst possible fatigue).

Rows: at Baseline, at Week 4, at Week 8

Outcome measures

Measure	Placebo n=11 Participants Participants who receive Placebo in Period 1	Acthar n=25 Participants Participants who receive Acthar in Period 1
Krupp Fatigue Severity Score (FSS) Within 8 Weeks at Baseline	5.374 score on a scale Standard Deviation 0.9840	5.648 score on a scale Standard Deviation 1.3091
Krupp Fatigue Severity Score (FSS) Within 8 Weeks at Week 4	5.379 score on a scale Standard Deviation 1.0697	5.298 score on a scale Standard Deviation 1.5401
Krupp Fatigue Severity Score (FSS) Within 8 Weeks at Week 8	5.404 score on a scale Standard Deviation 1.1699	5.152 score on a scale Standard Deviation 1.7858

SECONDARY outcome

Timeframe: at Baseline, Week 4 and Week 8 (within 8 weeks)

Population: mITT

The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement.

Rows: at Baseline, at Week 4, at Week 8

Outcome measures

Measure	Placebo n=11 Participants Participants who receive Placebo in Period 1	Acthar n=25 Participants Participants who receive Acthar in Period 1
Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks at Baseline	32.927 score on a scale Standard Deviation 12.3561	31.526 score on a scale Standard Deviation 11.7065
Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks at Week 4	32.831 score on a scale Standard Deviation 13.5390	35.318 score on a scale Standard Deviation 12.5159
Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks at Week 8	33.310 score on a scale Standard Deviation 12.9760	35.701 score on a scale Standard Deviation 11.8032

SECONDARY outcome

Timeframe: at Baseline, Week 4 and Week 8 (within 8 weeks)

Population: mITT

The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement.

Outcome measures

Measure	Placebo n=11 Participants Participants who receive Placebo in Period 1	Acthar n=25 Participants Participants who receive Acthar in Period 1
Mean Score on the Mental Component Scale (MCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks at Baseline	41.304 score on a scale Standard Deviation 11.8440	38.406 score on a scale Standard Deviation 14.6618
Mean Score on the Mental Component Scale (MCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks at Week 4	38.744 score on a scale Standard Deviation 16.8434	40.280 score on a scale Standard Deviation 13.0274
Mean Score on the Mental Component Scale (MCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks at Week 8	39.256 score on a scale Standard Deviation 18.4576	40.408 score on a scale Standard Deviation 15.8738

SECONDARY outcome

Timeframe: at Week 52

Population: mITT with necessary data at Week 52

Participants are counted as responders based on:

• decrease in SELENA-SLEDAI score from 4 to 0 for arthritis and no worsening in other organ systems based on BILAG

OR

• decrease in SELENA-SLEDAI score from 2 to 0 for rash and no worsening in other organ systems based on BILAG

Outcome measures

Measure	Placebo n=7 Participants Participants who receive Placebo in Period 1	Acthar n=13 Participants Participants who receive Acthar in Period 1
Number of Participants Who Meet the Definition of a Responder at Week 52	4 Participants	3 Participants

SECONDARY outcome

Timeframe: at Week 52

Population: mITT with necessary data at Week 52

SLEDAI was modeled on the basis of clinician global judgment. A participant's SELENA-SLEDAI total score is the sum of all marked SLE-related descriptors on a checklist developed by the SELENA Group (also referred to as hybrid SLEDAI).

The scores of the descriptors range from 0 to 8. A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity.

Outcome measures

Measure	Placebo n=7 Participants Participants who receive Placebo in Period 1	Acthar n=13 Participants Participants who receive Acthar in Period 1
Score on the SELENA-SLEDAI at Week 52	3 score on a scale Interval 0.0 to 8.0	4 score on a scale Interval 0.0 to 10.0

SECONDARY outcome

Timeframe: at Week 52

Population: mITT with necessary data at Week 52

PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.

Outcome measures

Measure	Placebo n=11 Participants Participants who receive Placebo in Period 1	Acthar n=22 Participants Participants who receive Acthar in Period 1
Physician's Global Assessment (PGA) of Disease Severity at Week 52 None	0 Participants	4 Participants
Physician's Global Assessment (PGA) of Disease Severity at Week 52 Mild	7 Participants	7 Participants
Physician's Global Assessment (PGA) of Disease Severity at Week 52 Moderate	0 Participants	2 Participants
Physician's Global Assessment (PGA) of Disease Severity at Week 52 Severe	0 Participants	0 Participants
Physician's Global Assessment (PGA) of Disease Severity at Week 52 Missing	4 Participants	9 Participants

SECONDARY outcome

Timeframe: at Week 52

Population: mITT with necessary data at Week 52

The doctor counted the number of tender or swollen joints at Week 52.

Outcome measures

Measure	Placebo n=7 Participants Participants who receive Placebo in Period 1	Acthar n=13 Participants Participants who receive Acthar in Period 1
Number of Tender or Swollen Joints at Week 52	1.1 Tender or Swollen Joints Standard Deviation 2.27	0.7 Tender or Swollen Joints Standard Deviation 2.21

SECONDARY outcome

Timeframe: at Week 52

Population: mITT with necessary data at Week 52

The CLASI consists of two scores the first summarizes the activity of the disease while the second is a measure of the damage done by the disease. Activity is scored on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The CLASI score ranges from 0 to 70, with higher scores indicating more severe skin disease.

Outcome measures

Measure	Placebo n=7 Participants Participants who receive Placebo in Period 1	Acthar n=13 Participants Participants who receive Acthar in Period 1
Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) at Week 52	0.4 score on a scale Standard Deviation 0.79	1.3 score on a scale Standard Deviation 1.55

SECONDARY outcome

Timeframe: at Week 52

Population: mITT with necessary data at Week 52

The Krupp FSS is a scale to rate disability-related fatigue. Respondents use a scale ranging from 1 ("completely disagree") to 7 ("completely agree") to indicate their agreement with nine statements about fatigue. A visual analogue scale is also included with the scale; respondents are asked to denote the severity of their fatigue over the past 2 weeks by placing a mark on a line extending from "no fatigue" to "fatigue as bad as could be." Higher scores on the scale are indicative of more severe fatigue.

This validated fatigue severity scale measures impact of fatigue with a 9-item questionnaire, with a 7-point Likert scale for each question. Total score ranges from 0 (best possible outcome) to 63 (worst possible fatigue).

Outcome measures

Measure	Placebo n=7 Participants Participants who receive Placebo in Period 1	Acthar n=13 Participants Participants who receive Acthar in Period 1
Krupp Fatigue Severity Score (FSS) at Week 52	4.523 score on a scale Standard Deviation 1.5491	4.743 score on a scale Standard Deviation 2.0428

SECONDARY outcome

Timeframe: at Week 52

Population: mITT with necessary data at Week 52

The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement.

Outcome measures

Measure	Placebo n=6 Participants Participants who receive Placebo in Period 1	Acthar n=13 Participants Participants who receive Acthar in Period 1
Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) at Week 52	43.618 score on a scale Standard Deviation 11.9596	39.710 score on a scale Standard Deviation 10.8066

SECONDARY outcome

Timeframe: at Week 52

Population: mITT with necessary data at Week 52

The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement.

Outcome measures

Measure	Placebo n=6 Participants Participants who receive Placebo in Period 1	Acthar n=13 Participants Participants who receive Acthar in Period 1
Mean Score on the Mental Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) at Week 52	45.272 score on a scale Standard Deviation 12.6597	39.700 score on a scale Standard Deviation 16.3027

SECONDARY outcome

Timeframe: within 52 weeks

Population: mITT with necessary data at Week 52

Outcome measures

Measure	Placebo n=5 Participants Participants who receive Placebo in Period 1	Acthar n=19 Participants Participants who receive Acthar in Period 1
Number of Participants With a Relapse Within 52 Weeks	1 Participants	6 Participants

Adverse Events

Period 1: Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Period 1: Acthar

Serious events: 3 serious events

Other events: 19 other events

Deaths: 0 deaths

Period 2: Placebo/Acthar

Serious events: 4 serious events

Other events: 8 other events

Deaths: 0 deaths

Period 2: Acthar/Acthar

Serious events: 2 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Measure	Period 1: Placebo n=11 participants at risk Participants who receive Placebo in Period 1	Period 1: Acthar n=25 participants at risk Participants who receive Acthar in Period 1	Period 2: Placebo/Acthar n=11 participants at risk Participants who receive Placebo in Period 1, but Acthar in Period 2	Period 2: Acthar/Acthar n=22 participants at risk Participants who receive Acthar in both Periods 1 and 2
Gastrointestinal disorders Abdominal pain lower	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
General disorders Non-cardiac chest pain	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Pelvic abscess	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Pelvic infection	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Pyelonephritis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
General disorders Chest discomfort	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
General disorders Multi-organ failure	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Klebsiella sepsis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Necrotising fasciitis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Viral infection	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations Liver function test abnormal	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Reproductive system and breast disorders Haemorrhagic ovarian cyst	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.

Other adverse events

Measure	Period 1: Placebo n=11 participants at risk Participants who receive Placebo in Period 1	Period 1: Acthar n=25 participants at risk Participants who receive Acthar in Period 1	Period 2: Placebo/Acthar n=11 participants at risk Participants who receive Placebo in Period 1, but Acthar in Period 2	Period 2: Acthar/Acthar n=22 participants at risk Participants who receive Acthar in both Periods 1 and 2
Infections and infestations Bronchitis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Gastroenteritis viral	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Nasopharyngitis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Oral candidiasis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	18.2% 2/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Oral herpes	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Pelvic abscess	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Pelvic infection	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Pneumonia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Pyelonephritis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Urinary tract infection	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	18.2% 2/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	13.6% 3/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Urinary tract infection bacterial	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Urinary tract infection staphylococcal	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Vaginitis bacterial	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Blood and lymphatic system disorders Anaemia	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Blood and lymphatic system disorders Leukopenia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Eye disorders Conjunctivitis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Eye disorders Diplopia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Eye disorders Keratitis	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Gastrointestinal disorders Abdominal pain	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	8.0% 2/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Gastrointestinal disorders Diarrhoea	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	8.0% 2/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Gastrointestinal disorders Dyspepsia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Gastrointestinal disorders Glossodynia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Gastrointestinal disorders Nausea	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Gastrointestinal disorders Swollen tongue	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Gastrointestinal disorders Vomiting	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
General disorders Asthenia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
General disorders Chest discomfort	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
General disorders Fatigue	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	8.0% 2/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
General disorders Injection site haematoma	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
General disorders Irritability	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	8.0% 2/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
General disorders Multi-organ failure	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
General disorders Non-cardiac chest pain	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
General disorders Oedema peripheral	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	13.6% 3/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
General disorders Thirst	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Ear infection	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Gastroenteritis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Influenza	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Klebsiella sepsis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Necrotising fasciitis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Sinusitis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Upper respiratory tract infection	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Viral infection	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Infections and infestations Vulvovaginal mycotic infection	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Injury, poisoning and procedural complications Burns first degree	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Injury, poisoning and procedural complications Femur fracture	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations Blood potassium decreased	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 2/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations Blood pressure diastolic increased	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations Blood pressure increased	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations False positive investigation result	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations International normalised ratio increased	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations Liver function test abnormal	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations Occult blood positive	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations Weight increased	18.2% 2/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	20.0% 5/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Metabolism and nutrition disorders Fluid retention	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	8.0% 2/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Metabolism and nutrition disorders Glucose tolerance impaired	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Metabolism and nutrition disorders Hypokalaemia	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	8.0% 2/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Blood and lymphatic system disorders Microcytic anaemia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Cardiac disorders Tachycardia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Ear and labyrinth disorders Ear haemorrhage	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Eye disorders Dry eye	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Eye disorders Retinal degeneration	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Eye disorders Ulcerative keratitis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Eye disorders Vision blurred	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Eye disorders Visual impairment	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Gastrointestinal disorders Rectal prolapse	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
General disorders Injection site pain	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
General disorders Nodule	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Injury, poisoning and procedural complications Laceration	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 2/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations Blood creatinine increased	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations Blood phosphorus decreased	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations Computerised tomogram thorax abnormal	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations Glycosylated haemoglobin increased	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations Haematocrit decreased	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Investigations Percussion test abnormal	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	13.6% 3/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Musculoskeletal and connective tissue disorders Osteopenia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Musculoskeletal and connective tissue disorders Synovitis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Nervous system disorders Dizziness	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Nervous system disorders Headache	18.2% 2/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 2/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Nervous system disorders Sciatica	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Psychiatric disorders Anxiety	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Psychiatric disorders Mood swings	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	8.0% 2/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Psychiatric disorders Nervousness	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Renal and urinary disorders Dysuria	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Renal and urinary disorders Nephrolithiasis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 2/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Reproductive system and breast disorders Vulvovaginal discomfort	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Respiratory, thoracic and mediastinal disorders Cough	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Respiratory, thoracic and mediastinal disorders Pharyngeal erythema	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Respiratory, thoracic and mediastinal disorders Pleural rub	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	18.2% 2/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 2/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Skin and subcutaneous tissue disorders Increased tendency to bruise	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Skin and subcutaneous tissue disorders Rash	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Vascular disorders Extremity necrosis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Vascular disorders Hypertension	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.5% 1/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Vascular disorders Phlebitis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	9.1% 1/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Nervous system disorders Dysgeusia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Nervous system disorders Hypoaesthesia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Nervous system disorders Lethargy	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Nervous system disorders Migraine	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Nervous system disorders Polyneuropathy	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Nervous system disorders Tremor	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Psychiatric disorders Abnormal behaviour	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Psychiatric disorders Insomnia	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Reproductive system and breast disorders Haemorrhagic ovarian cyst	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	8.0% 2/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Skin and subcutaneous tissue disorders Blister	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Skin and subcutaneous tissue disorders Hypertrichosis	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Skin and subcutaneous tissue disorders Photosensitivity reaction	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	4.0% 1/25 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/11 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.	0.00% 0/22 • Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.

Additional Information

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