Trial Outcomes & Findings for Study of Acthar® Gel (Acthar) for Amyotrophic Lateral Sclerosis (ALS) (NCT NCT03068754)

Last Updated: 2020-10-14

Results Overview

The ALSFRS-R is a validated questionnaire-based scale used extensively as a primary outcome measure in ALS clinical trials and is considered a predictor of survival. ALSFRS-R is a 12-item scale that measures 4 domains relevant for ALS (gross motor, fine motor, bulbar and respiratory) A trained, independent rater calls each participant (or the caregiver) to administer the questionnaire. The 12 functions are rated on a scale from 0 to 4, with a highest possible (summed) score of 48. Higher scores represent better function.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

143 participants

Primary outcome timeframe

Baseline, Week 36

Results posted on

2020-10-14

Participant Flow

Of 207 potential participants screened, 143 were randomized to begin treatment

Participant milestones

Participant milestones
Measure	Arm A: Randomized Treatment Period (RTP) Acthar Gel Participants receive one 0.2 mL subcutaneous (SC) injection (shot under the skin) of the study drug (Acthar Gel), daily for up to 36 weeks. Those who do not continue into the extension period had 3 weeks of tapering off the drug, ending their participation by Week 39.	Arm B: RTP Placebo Participants receive one 0.2 mL SC injection that looks like Acthar, but has no drug in it (matching Placebo), daily for up to 36 weeks. Those who do not continue into the extension period had 3 weeks of simulated tapering, ending their participation by Week 39.	Arm C: Open Label Extension Period (OLE) Acthar Gel-Acthar Gel Participants who received Acthar Gel during the treatment period and continue into the extension period do not go through the treatment-period tapering, but receive one 0.2 mL SC injection of Acthar Gel, daily for up to 48 weeks, followed by 3 weeks of tapering off the drug, ending their participation within about 21 months.	Arm D: OLE Placebo-Acthar Gel Participants who received Placebo during the treatment period and continue into the extension period do not go through the treatment-period simulated tapering, but receive one 0.2 mL SC injection of Acthar, daily for up to 48 weeks, followed by 3 weeks of tapering off the drug, ending their participation within about 21 months.
Randomized Treatment Period (RTP) STARTED	95	48	0	0
Randomized Treatment Period (RTP) Intention to Treat (ITT) Population	95	48	0	0
Randomized Treatment Period (RTP) Safety Population	95	47	0	0
Randomized Treatment Period (RTP) Modified ITT (mITT)	93	46	0	0
Randomized Treatment Period (RTP) Completed Taper	58	28	0	0
Randomized Treatment Period (RTP) Completed 36 Weeks of Treatment	28	9	0	0
Randomized Treatment Period (RTP) Completed RTP	27	9	0	0
Randomized Treatment Period (RTP) Enrolled in OLE Period	25	8	0	0
Randomized Treatment Period (RTP) COMPLETED	28	9	0	0
Randomized Treatment Period (RTP) NOT COMPLETED	67	39	0	0
Open Label Extension Period (OLE) STARTED	0	0	25	8
Open Label Extension Period (OLE) Completed Taper	0	0	19	7
Open Label Extension Period (OLE) Completed OLE Period	0	0	3	2
Open Label Extension Period (OLE) Completed Treatment in OLE	0	0	4	2
Open Label Extension Period (OLE) COMPLETED	0	0	4	2
Open Label Extension Period (OLE) NOT COMPLETED	0	0	21	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Randomized Treatment Period (RTP) Acthar Gel Participants receive one 0.2 mL subcutaneous (SC) injection (shot under the skin) of the study drug (Acthar Gel), daily for up to 36 weeks. Those who do not continue into the extension period had 3 weeks of tapering off the drug, ending their participation by Week 39.	Arm B: RTP Placebo Participants receive one 0.2 mL SC injection that looks like Acthar, but has no drug in it (matching Placebo), daily for up to 36 weeks. Those who do not continue into the extension period had 3 weeks of simulated tapering, ending their participation by Week 39.	Arm C: Open Label Extension Period (OLE) Acthar Gel-Acthar Gel Participants who received Acthar Gel during the treatment period and continue into the extension period do not go through the treatment-period tapering, but receive one 0.2 mL SC injection of Acthar Gel, daily for up to 48 weeks, followed by 3 weeks of tapering off the drug, ending their participation within about 21 months.	Arm D: OLE Placebo-Acthar Gel Participants who received Placebo during the treatment period and continue into the extension period do not go through the treatment-period simulated tapering, but receive one 0.2 mL SC injection of Acthar, daily for up to 48 weeks, followed by 3 weeks of tapering off the drug, ending their participation within about 21 months.
Randomized Treatment Period (RTP) Adverse Event	1	3	0	0
Randomized Treatment Period (RTP) Death	2	2	0	0
Randomized Treatment Period (RTP) Disease progression	1	2	0	0
Randomized Treatment Period (RTP) Lost to Follow-up	1	0	0	0
Randomized Treatment Period (RTP) Withdrawal by Subject	6	2	0	0
Randomized Treatment Period (RTP) Discontinued by Physician	1	0	0	0
Randomized Treatment Period (RTP) Subject Decision based on Compensation	0	1	0	0
Randomized Treatment Period (RTP) Trial Terminated by Sponsor	55	29	0	0
Open Label Extension Period (OLE) Adverse Event	0	0	0	1
Open Label Extension Period (OLE) Death	0	0	0	1
Open Label Extension Period (OLE) Disease progression	0	0	3	1
Open Label Extension Period (OLE) Withdrawal by Subject	0	0	5	0
Open Label Extension Period (OLE) Subject Discontinued for Non-efficacy	0	0	1	0
Open Label Extension Period (OLE) Trial Terminated by Sponsor	0	0	12	3

Baseline Characteristics

Study of Acthar® Gel (Acthar) for Amyotrophic Lateral Sclerosis (ALS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: RTP Acthar Gel n=95 Participants Participants receive one 0.2 mL subcutaneous (SC) injection (shot under the skin) of the study drug (Acthar Gel), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of tapering off the drug, ending their participation by Week 39.	Arm B: RTP Placebo n=47 Participants Participants receive one 0.2 mL SC injection that looks like Acthar, but has no drug in it (matching Placebo), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of simulated tapering, ending their participation by Week 39.	Total n=142 Participants Total of all reporting groups
Age, Continuous	55.9 years STANDARD_DEVIATION 10.80 • n=5 Participants	56.3 years STANDARD_DEVIATION 10.68 • n=7 Participants	56.0 years STANDARD_DEVIATION 10.72 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	21 Participants n=7 Participants	56 Participants n=5 Participants
Sex: Female, Male Male	60 Participants n=5 Participants	26 Participants n=7 Participants	86 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	38 Participants n=5 Participants	19 Participants n=7 Participants	57 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	57 Participants n=5 Participants	28 Participants n=7 Participants	85 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	72 Participants n=5 Participants	33 Participants n=7 Participants	105 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 36

Population: Safety Population

Outcome measures

Outcome measures
Measure	Arm A: RTP Acthar Gel n=95 Participants Participants receive one 0.2 mL subcutaneous (SC) injection (shot under the skin) of the study drug (Acthar Gel), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of tapering off the drug, ending their participation by Week 39.	Arm B: RTP Placebo n=47 Participants Participants receive one 0.2 mL SC injection that looks like Acthar, but has no drug in it (matching Placebo), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of simulated tapering, ending their participation by Week 39.
Treatment Period: Scores on a Scale for Telephone-administered Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Baseline	34.7 score on a scale Standard Deviation 6.01	34.3 score on a scale Standard Deviation 5.84
Treatment Period: Scores on a Scale for Telephone-administered Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Week 36	26.4 score on a scale Standard Deviation 9.34	30.8 score on a scale Standard Deviation 7.55

PRIMARY outcome

Timeframe: by the end of the treatment period (within 36 Weeks)

Population: Safety Population

Serious adverse events, non-serious treatment-emergent adverse events, and all-cause mortality are collected until the participant no longer participates in the study Clinically significant changes in safety measures are recorded as adverse events.

Outcome measures

Outcome measures
Measure	Arm A: RTP Acthar Gel n=95 Participants Participants receive one 0.2 mL subcutaneous (SC) injection (shot under the skin) of the study drug (Acthar Gel), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of tapering off the drug, ending their participation by Week 39.	Arm B: RTP Placebo n=47 Participants Participants receive one 0.2 mL SC injection that looks like Acthar, but has no drug in it (matching Placebo), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of simulated tapering, ending their participation by Week 39.
Number of Participants Experiencing an Adverse Event During the Treatment Period Serious Treatment Emergent Adverse Events	13 Participants	6 Participants
Number of Participants Experiencing an Adverse Event During the Treatment Period Non-serious Treatment-Emergent Adverse Events	74 Participants	40 Participants
Number of Participants Experiencing an Adverse Event During the Treatment Period Death	2 Participants	3 Participants

PRIMARY outcome

Timeframe: by the time of database lock (within 84 weeks)

Population: Safety Population

Serious adverse events, non-serious treatment-emergent adverse events, and all-cause mortality are collected until the participant no longer participates in the study (estimated about 1 year for participants leaving after the treatment period, and two years for participants who participate also in the open label extension). Clinically significant changes in safety measures are recorded as adverse events.

Outcome measures

Outcome measures
Measure	Arm A: RTP Acthar Gel n=25 Participants Participants receive one 0.2 mL subcutaneous (SC) injection (shot under the skin) of the study drug (Acthar Gel), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of tapering off the drug, ending their participation by Week 39.	Arm B: RTP Placebo n=8 Participants Participants receive one 0.2 mL SC injection that looks like Acthar, but has no drug in it (matching Placebo), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of simulated tapering, ending their participation by Week 39.
Number of Participants Experiencing an Adverse Event by the End of the Trial in the OLE Period Serious Treatment Emergent Adverse Events	4 Participants	2 Participants
Number of Participants Experiencing an Adverse Event by the End of the Trial in the OLE Period Non-serious Treatment-Emergent Adverse Events	20 Participants	7 Participants

SECONDARY outcome

Timeframe: Baseline, Week 36

Population: Safety population

Spirometry (meaning the measuring of breath) is the most common of the lung function tests. It measures how much air can be inhaled \[Forced Vital Capacity (FVC)\] and exhaled \[(Forced Expiratory Volume in one second (FEV1)\].

Outcome measures

Outcome measures
Measure	Arm A: RTP Acthar Gel n=95 Participants Participants receive one 0.2 mL subcutaneous (SC) injection (shot under the skin) of the study drug (Acthar Gel), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of tapering off the drug, ending their participation by Week 39.	Arm B: RTP Placebo n=47 Participants Participants receive one 0.2 mL SC injection that looks like Acthar, but has no drug in it (matching Placebo), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of simulated tapering, ending their participation by Week 39.
Treatment Period: Spirometry (%) FVC at Baseline	85.0 liters Standard Deviation 18.31	82.1 liters Standard Deviation 17.60
Treatment Period: Spirometry (%) FVC at Week 36	61.4 liters Standard Deviation 27.37	63.8 liters Standard Deviation 26.05
Treatment Period: Spirometry (%) FEV1 at Baseline	79.3 liters Standard Deviation 18.78	77.8 liters Standard Deviation 18.52
Treatment Period: Spirometry (%) FEV1 at Week 36	59.1 liters Standard Deviation 27.37	54.3 liters Standard Deviation 26.79

SECONDARY outcome

Timeframe: Baseline, Week 36

Population: Safety Population, with an actual score at the given time point

The ALSFRS-R is a 12-item scale evaluating 4 domains relevant to ALS (gross motor, fine motor, bulbar and respiratory). The trained investigator (or designee) administers the ALSFRS-R questionnaire in person with the participant (or caregiver). The 12 functions are rated on a scale from 0 to 4, with a highest possible (summed) score of 48. Higher scores represent better function.

Outcome measures

Outcome measures
Measure	Arm A: RTP Acthar Gel n=95 Participants Participants receive one 0.2 mL subcutaneous (SC) injection (shot under the skin) of the study drug (Acthar Gel), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of tapering off the drug, ending their participation by Week 39.	Arm B: RTP Placebo n=47 Participants Participants receive one 0.2 mL SC injection that looks like Acthar, but has no drug in it (matching Placebo), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of simulated tapering, ending their participation by Week 39.
Treatment Period: Scores on a Scale for Investigator-administered ALSFRS-R Week 36	28.0 score on a scale Standard Deviation 9.50	30.9 score on a scale Standard Deviation 7.18
Treatment Period: Scores on a Scale for Investigator-administered ALSFRS-R Baseline	35.8 score on a scale Standard Deviation 6.05	35.4 score on a scale Standard Deviation 6.23

SECONDARY outcome

Timeframe: Baseline, Week 84

Population: OLE population with scores at the given week; baseline is defined as the value at randomization (week 0)

The ALSFRS-R is a 12-item scale evaluating 4 domains relevant to ALS (gross motor, fine motor, bulbar and respiratory). The trained investigator (or designee) administers the ALSFRS-R questionnaire in person with the participant (or caregiver). The 12 functions are rated on a scale from 0 to 4, with a highest possible score of 48. Higher scores represent better function.

Outcome measures

Outcome measures
Measure	Arm A: RTP Acthar Gel n=25 Participants Participants receive one 0.2 mL subcutaneous (SC) injection (shot under the skin) of the study drug (Acthar Gel), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of tapering off the drug, ending their participation by Week 39.	Arm B: RTP Placebo n=7 Participants Participants receive one 0.2 mL SC injection that looks like Acthar, but has no drug in it (matching Placebo), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of simulated tapering, ending their participation by Week 39.
Extension Period: Scores on a Scale for Investigator-administered ALSFRS-R Baseline	36.8 units on a scale Standard Deviation 5.33	39.6 units on a scale Standard Deviation 1.81
Extension Period: Scores on a Scale for Investigator-administered ALSFRS-R Week 84	27.4 units on a scale Standard Deviation 5.41	21.5 units on a scale Standard Deviation 4.95

Adverse Events

Arm A: RTP Acthar Gel

Serious events: 13 serious events

Other events: 71 other events

Deaths: 2 deaths

Arm B: RTP Placebo

Serious events: 6 serious events

Other events: 34 other events

Deaths: 3 deaths

Arm C: OLE Acthar Gel-Acthar Gel

Serious events: 4 serious events

Other events: 18 other events

Deaths: 1 deaths

Arm D: OLE Placebo-Acthar Gel

Serious events: 2 serious events

Other events: 7 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Information Call Center

Mallinckrodt

Phone: 800-556-3314

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Arm A: RTP Acthar Gel n=95 participants at risk Participants receive one 0.2 mL subcutaneous (SC) injection (shot under the skin) of the study drug (Acthar Gel), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of tapering off the drug, ending their participation by Week 39.	Arm B: RTP Placebo n=47 participants at risk Participants receive one 0.2 mL SC injection that looks like Acthar, but has no drug in it (matching Placebo), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of simulated tapering, ending their participation by Week 39.	Arm C: OLE Acthar Gel-Acthar Gel n=25 participants at risk Participants who receive Acthar Gel during the treatment period and continue into the extension period do not go through the treatment-period tapering, but receive one 0.2 mL SC injection of Acthar Gel, daily for up to 48 weeks, followed by 3 weeks of tapering off the drug, ending their participation within about 21 months.	Arm D: OLE Placebo-Acthar Gel n=8 participants at risk Participants who receive Placebo during the treatment period and continue into the extension period do not go through the treatment-period simulated tapering, but receive one 0.2 mL SC injection of Acthar, daily for up to 48 weeks, followed by 3 weeks of tapering off the drug, ending their participation within about 21 months.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	2.1% 2/95 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.1% 2/95 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.1% 2/95 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Respiratory, thoracic and mediastinal disorders Haemothorax	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Infections and infestations Pneumonia	6.3% 6/95 • Number of events 6 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Infections and infestations Cellulitis staphylococcal	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Infections and infestations Empyema	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Infections and infestations Gastroenteritis	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Infections and infestations Pyelonephritis acute	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Infections and infestations Respiratory tract infection	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Infections and infestations Urosepsis	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Injury, poisoning and procedural complications Procedural pain	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Injury, poisoning and procedural complications Rib fracture	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Metabolism and nutrition disorders Dehydration	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Metabolism and nutrition disorders Failure to thrive	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Nervous system disorders Amyotrophic lateral sclerosis	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Nervous system disorders Cerebellar infarction	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Psychiatric disorders Anxiety	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Psychiatric disorders Depression	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Vascular disorders Deep vein thrombosis	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Vascular disorders Hypertensive emergency	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
General disorders Gait disturbance	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Injury, poisoning and procedural complications Fall	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Psychiatric disorders Mental status changes	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Psychiatric disorders Suicidal ideation	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Gastrointestinal disorders Constipation	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.

Other adverse events
Measure	Arm A: RTP Acthar Gel n=95 participants at risk Participants receive one 0.2 mL subcutaneous (SC) injection (shot under the skin) of the study drug (Acthar Gel), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of tapering off the drug, ending their participation by Week 39.	Arm B: RTP Placebo n=47 participants at risk Participants receive one 0.2 mL SC injection that looks like Acthar, but has no drug in it (matching Placebo), daily for up to 36 weeks. Those who do not continue into the extension period will have 3 weeks of simulated tapering, ending their participation by Week 39.	Arm C: OLE Acthar Gel-Acthar Gel n=25 participants at risk Participants who receive Acthar Gel during the treatment period and continue into the extension period do not go through the treatment-period tapering, but receive one 0.2 mL SC injection of Acthar Gel, daily for up to 48 weeks, followed by 3 weeks of tapering off the drug, ending their participation within about 21 months.	Arm D: OLE Placebo-Acthar Gel n=8 participants at risk Participants who receive Placebo during the treatment period and continue into the extension period do not go through the treatment-period simulated tapering, but receive one 0.2 mL SC injection of Acthar, daily for up to 48 weeks, followed by 3 weeks of tapering off the drug, ending their participation within about 21 months.
Gastrointestinal disorders Constipation	13.7% 13/95 • Number of events 15 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	8.5% 4/47 • Number of events 5 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	8.0% 2/25 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	25.0% 2/8 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Gastrointestinal disorders Dry Mouth	5.3% 5/95 • Number of events 5 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Gastrointestinal disorders Dysphagia	5.3% 5/95 • Number of events 5 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	10.6% 5/47 • Number of events 5 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Gastrointestinal disorders Nausea	5.3% 5/95 • Number of events 6 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.3% 2/47 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	8.0% 2/25 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Gastrointestinal disorders Salivary hypersecretion	5.3% 5/95 • Number of events 6 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
General disorders Asthenia	6.3% 6/95 • Number of events 7 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	8.5% 4/47 • Number of events 5 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
General disorders Fatigue	13.7% 13/95 • Number of events 14 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.8% 6/47 • Number of events 8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.0% 3/25 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
General disorders Injection site bruising	13.7% 13/95 • Number of events 16 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	8.5% 4/47 • Number of events 6 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
General disorders Oedema	5.3% 5/95 • Number of events 5 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
General disorders Oedema peripheral	17.9% 17/95 • Number of events 24 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.3% 2/47 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	8.0% 2/25 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	25.0% 2/8 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Infections and infestations Gastroenteritis viral	2.1% 2/95 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	6.4% 3/47 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Infections and infestations Urinary tract infection	8.4% 8/95 • Number of events 12 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.3% 2/47 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	16.0% 4/25 • Number of events 6 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Injury, poisoning and procedural complications Contusion	9.5% 9/95 • Number of events 14 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.3% 2/47 • Number of events 4 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	8.0% 2/25 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Injury, poisoning and procedural complications Fall	18.9% 18/95 • Number of events 28 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	29.8% 14/47 • Number of events 33 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	24.0% 6/25 • Number of events 11 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Injury, poisoning and procedural complications Laceration	1.1% 1/95 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	6.4% 3/47 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Investigations Blood pressure increased	5.3% 5/95 • Number of events 7 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Investigations Weight decreased	3.2% 3/95 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	10.6% 5/47 • Number of events 6 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Metabolism and nutrition disorders Increased appetite	5.3% 5/95 • Number of events 6 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Musculoskeletal and connective tissue disorders Arthralgia	8.4% 8/95 • Number of events 16 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	8.5% 4/47 • Number of events 8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Musculoskeletal and connective tissue disorders Muscle atrophy	2.1% 2/95 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	6.4% 3/47 • Number of events 5 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.0% 3/25 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Musculoskeletal and connective tissue disorders Muscle spasms	15.8% 15/95 • Number of events 16 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	6.4% 3/47 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	8.0% 2/25 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Musculoskeletal and connective tissue disorders Muscular weakness	23.2% 22/95 • Number of events 35 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	19.1% 9/47 • Number of events 14 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.0% 3/25 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	25.0% 2/8 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	4.2% 4/95 • Number of events 6 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	14.9% 7/47 • Number of events 7 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Musculoskeletal and connective tissue disorders Neck Pain	5.3% 5/95 • Number of events 5 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Musculoskeletal and connective tissue disorders Pain in extremity	3.2% 3/95 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	6.4% 3/47 • Number of events 4 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	25.0% 2/8 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Nervous system disorders Dizziness	7.4% 7/95 • Number of events 7 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	6.4% 3/47 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Nervous system disorders Dysarthria	9.5% 9/95 • Number of events 12 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	8.5% 4/47 • Number of events 5 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Nervous system disorders Headache	11.6% 11/95 • Number of events 14 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 6 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	25.0% 2/8 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Nervous system disorders Muscle contractions involuntary	3.2% 3/95 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	6.4% 3/47 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	8.0% 2/25 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Psychiatric disorders Anxiety	6.3% 6/95 • Number of events 6 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.3% 2/47 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Psychiatric disorders Depression	3.2% 3/95 • Number of events 4 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	6.4% 3/47 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.5% 9/95 • Number of events 10 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.8% 6/47 • Number of events 8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	25.0% 2/8 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Skin and subcutaneous tissue disorders Ecchymosis	5.3% 5/95 • Number of events 5 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.3% 2/47 • Number of events 3 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Vascular disorders Hypertension	8.4% 8/95 • Number of events 10 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	2.1% 1/47 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Cardiac disorders Tachycardia	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	8.0% 2/25 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Ear and labyrinth disorders Excessive cerumen production	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Gastrointestinal disorders Diarrhoea	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	4.0% 1/25 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	25.0% 2/8 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Gastrointestinal disorders Inflammatory bowel disease	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/25 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	12.5% 1/8 • Number of events 1 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.
Gastrointestinal disorders Vomiting	0.00% 0/95 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/47 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	8.0% 2/25 • Number of events 2 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.	0.00% 0/8 • From the start to the end of the period; RTP is 36 weeks (plus 3 weeks if ending there), OLE is up to 21 months (up to Week 84) Treatment-emergent adverse events (TEAEs) were collected. A TEAE is defined as an adverse event that starts or worsens on or after first dose of study drug and within 28 days from the last dose date of the study drug (For subjects entered into OLE, any TEAE started prior to first OLE dose is counted in RTP). For each system organ class and preferred term, subjects are counted only once, even if they experienced multiple events in that system organ class or preferred term.