Trial Outcomes & Findings for Phase III Study of Edasalonexent in Boys With Duchenne Muscular Dystrophy (NCT NCT03703882)

Last Updated: 2022-06-21

Results Overview

To assess change from baseline in North Star Ambulatory Assessment(NSAA) Total Score at Wk52. NSAA is clinician-reported outcome instrument designed to measure ambulatory function in males with Duchenne muscular dystrophy(DMD). Patients asked to perform 17 different functional activities,including 10MWT,rising from sit to stand,standing on one leg,climbing \& descending a step,stand from supine, lifting the head, standing on heels, \& jumping. Each function activity will be scored as0=(unable to achieve independently),scored as1=(modified method but achieves goal independent of physical assistance from another),or scored as2=(no obvious modification of activity)or "Not Scored". If NSAA test was performed \& any of the individual items are scored as "not scored"(i.e, for reasons unrelated to patients physical capabilities), corresponding total score will be set to missing. Sum of 17 scores will be used to form an ordinal total score(range 0-34).Higher scores imply better functional status

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

131 participants

Primary outcome timeframe

Baseline (Day 1) to Week 52

Results posted on

2022-06-21

Participant Flow

This was a multi-center study conducted by 37 principal investigators at 37 study centers in 8 countries (United States, Canada, United Kingdom, Germany, Ireland, Israel, Sweden, and Australia.)

A total of 151 patients were screened of which 20 failed screening. 131 patients who participated in the study included 126 randomized patients and 5 participants who were dosed siblings of previously randomized patients.

Participant milestones

Participant milestones
Measure	Dose 1 Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day. Edasalonexent: 100 mg/kg/day	Placebo Matching placebo Placebo: Placebo
Overall Study STARTED	88	43
Overall Study COMPLETED	85	37
Overall Study NOT COMPLETED	3	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose 1 Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day. Edasalonexent: 100 mg/kg/day	Placebo Matching placebo Placebo: Placebo
Overall Study Adverse Event	1	0
Overall Study Lost to Follow-up	0	2
Overall Study Non-compliance with study drug	0	1
Overall Study Physician Decision	0	1
Overall Study Progressive disease	1	0
Overall Study Withdrawal by parent/guardian	1	0
Overall Study Starting another treatment	0	1
Overall Study noncompliance with study procedures	0	1

Baseline Characteristics

Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose 1 n=88 Participants Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day. Edasalonexent: 100 mg/kg/day	Placebo n=43 Participants Matching placebo Placebo: Placebo	Total n=131 Participants Total of all reporting groups
Age, Continuous	5.65 years STANDARD_DEVIATION 1.048 • n=88 Participants	5.77 years STANDARD_DEVIATION 0.995 • n=43 Participants	5.69 years STANDARD_DEVIATION 1.029 • n=131 Participants
Sex: Female, Male Female	0 Participants n=88 Participants	0 Participants n=43 Participants	0 Participants n=131 Participants
Sex: Female, Male Male	88 Participants n=88 Participants	43 Participants n=43 Participants	131 Participants n=131 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=88 Participants	6 Participants n=43 Participants	20 Participants n=131 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	69 Participants n=88 Participants	35 Participants n=43 Participants	104 Participants n=131 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=88 Participants	2 Participants n=43 Participants	7 Participants n=131 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=87 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.	0 Participants n=43 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.	0 Participants n=130 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.
Race (NIH/OMB) Asian	3 Participants n=87 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.	2 Participants n=43 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.	5 Participants n=130 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=87 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.	0 Participants n=43 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.	1 Participants n=130 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.
Race (NIH/OMB) Black or African American	4 Participants n=87 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.	1 Participants n=43 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.	5 Participants n=130 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.
Race (NIH/OMB) White	74 Participants n=87 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.	38 Participants n=43 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.	112 Participants n=130 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.
Race (NIH/OMB) More than one race	3 Participants n=87 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.	1 Participants n=43 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.	4 Participants n=130 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=87 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.	1 Participants n=43 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.	3 Participants n=130 Participants • Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial.

PRIMARY outcome

Timeframe: Baseline (Day 1) to Week 52

Population: Full Analysis population: All patients in the Randomized Population who received at least 1 dose of study drug and provided at least 1 valid post Baseline NSAA efficacy assessment.

Outcome measures

Outcome measures
Measure	Dose 1 n=81 Participants Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day. Edasalonexent: 100 mg/kg/day	Placebo n=38 Participants Matching placebo Placebo: Placebo
Change From Baseline in North Star Ambulatory Assessment (NSAA)	-1.5 score on a scale Standard Deviation 4.41	-1.8 score on a scale Standard Deviation 3.81

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 52

Population: Full Analysis population: All patients in the Randomized Population who received at least 1 dose of study drug and provided at least 1 valid post Baseline NSAA efficacy assessment.

To assess the changes from baseline to Week 52 on the 10-meter walk/run test (10MWT). For timed function tests (TFTs), the time will be set to 12 seconds and the speed to 0 if the TFT assessment meets the following TFT grading criteria. Grade of 1 or 2 (from a 6-point scale). 1=Unable to walk independently 2=Unable to walk independently but can walk with knee-ankle foot orthoses or support from a person 3=Highly adapted wide based lordotic gait. Cannot increase walking speed 4=Moderately adapted gait. Can pick up speed but cannot run 5=Able to pick up speed, but runs with a double stance phase, i.e. cannot achieve both feet off the ground 6=Runs and gets both feet off the ground (with no double stance phase)

Outcome measures

Outcome measures
Measure	Dose 1 n=81 Participants Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day. Edasalonexent: 100 mg/kg/day	Placebo n=38 Participants Matching placebo Placebo: Placebo
Change From Baseline in 10-meter Walk/Run Test	-0.0058 score on a scale Standard Deviation 0.03010	-0.0093 score on a scale Standard Deviation 0.02538

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 52

Population: Full Analysis population: All patients in the Randomized Population who received at least 1 dose of study drug and provided at least 1 valid post Baseline NSAA efficacy assessment.

To assess the change from baseline in the stand from supine speed at Week 52. For timed function tests (TFTs) , the time will be set to 12 seconds and the speed to 0 if the TFT assessment meets the following TFT grading criteria. Grade of 1 or 2 (from a 6-point scale). 1 = Unable to stand from supine, even with use of a chair, 2 = Assisted Gowers - requires furniture for assist in arising from supine to full upright posture (no time to be recorded) 3=Rolls over, stands up with both hands "climbing up" the legs to achieve full upright posture 4=Rolls over, stands up with 1 hand support on leg 5=Rolls to the side and stands up with one or both hands on the floor to start to rise but does not touch legs 6=Stands up without rolling over or using hands on legs or floor

Outcome measures

Outcome measures
Measure	Dose 1 n=81 Participants Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day. Edasalonexent: 100 mg/kg/day	Placebo n=38 Participants Matching placebo Placebo: Placebo
Change From Baseline in Time to Stand From Supine	-0.0389 score on a scale Standard Deviation 0.06728	-0.0459 score on a scale Standard Deviation 0.06171

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 52

Population: Full Analysis Population: All patients in the Randomized Population who received at least 1 dose of study drug and provided at least 1 valid post Baseline NSAA efficacy assessment).

To assess the change from baseline to Week 52 on the 4-Stair Climb. For timed function tests (TFTs) , the time will be set to 12 seconds and the speed to 0 if the TFT assessment meets the following TFT grading criteria. Grade of 1(from a 6-point scale)1=Unable to climb 4 standard stairs(no time recorded) 2=Climbs 4 standard stairs "marking time"(climbs one foot at a time, with both feet on a step before moving to next step), uses both arms on one or both handrails or uses 1 handrail and the other arm pushes on the leg 3=Climbs 4 standard stairs "marking time", using one arm on one handrail or one hand pushing on leg or body 4=Climbs 4 standard stairs "marking time", not needing handrail and not using hands to push on leg 5=Climbs 4 standard stairs alternating feet, needs handrail/s for support or uses arms to push on the leg or body 6=Climbs 4 standard stairs alternating feet, not needing handrail support or using arm to push on the leg

Outcome measures

Outcome measures
Measure	Dose 1 n=81 Participants Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day. Edasalonexent: 100 mg/kg/day	Placebo n=38 Participants Matching placebo Placebo: Placebo
Change From Baseline in 4-stair Climb	-0.0220 score on a scale Standard Deviation 0.08920	-0.0392 score on a scale Standard Deviation 0.07352

SECONDARY outcome

Timeframe: Up to Week 52

Population: Safety population: All patients who received at least 1 dose of study drug, with patients analyzed based on the actual study treatment received. This included the set of patients who were assigned the same treatment as their randomized sibling.

Adverse events that occurred from the time of the administration of the first dose of investigational product (IP) through the end of the safety follow-up were considered treatment-emergent AEs (TEAEs). Serious adverse event (SAE).

Outcome measures

Outcome measures
Measure	Dose 1 n=88 Participants Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day. Edasalonexent: 100 mg/kg/day	Placebo n=43 Participants Matching placebo Placebo: Placebo
Safety and Tolerability Measured by Number of Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Treatment Emergent Adverse Event (TEAEs)	85 participants	41 participants
Safety and Tolerability Measured by Number of Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Related Treatment Emergent Adverse Event (TEAEs)	61 participants	14 participants
Safety and Tolerability Measured by Number of Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Serious TEAE	1 participants	1 participants
Safety and Tolerability Measured by Number of Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Serious Related TEAEs	0 participants	0 participants
Safety and Tolerability Measured by Number of Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs Leading to Study Discontinuation	1 participants	0 participants
Safety and Tolerability Measured by Number of Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Treatment-Related TEAEs Leading to Study Discontinuation	1 participants	0 participants

Adverse Events

Dose 1

Serious events: 1 serious events

Other events: 85 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dose 1 n=88 participants at risk Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day. Edasalonexent: 100 mg/kg/day	Placebo n=43 participants at risk Matching placebo Placebo: Placebo
Infections and infestations Gastroenteritis norovirus	1.1% 1/88 • Number of events 1 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	0.00% 0/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Infections and infestations Bronchiolitis	0.00% 0/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	2.3% 1/43 • Number of events 1 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.

Other adverse events

Additional Information

Andrew Nichols, PhD - Chief Scientific Officer

Astria Therapeutics, Inc

Phone: 617-349-1971

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Dose 1 n=88 participants at risk Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day. Edasalonexent: 100 mg/kg/day	Placebo n=43 participants at risk Matching placebo Placebo: Placebo
Gastrointestinal disorders Diarrhoea	61.4% 54/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	27.9% 12/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Gastrointestinal disorders Vomiting	33.0% 29/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	25.6% 11/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Gastrointestinal disorders Abdominal pain upper	17.0% 15/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	20.9% 9/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Gastrointestinal disorders Nausea	8.0% 7/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	11.6% 5/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Gastrointestinal disorders Constipation	6.8% 6/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	7.0% 3/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Gastrointestinal disorders Abdominal pain	8.0% 7/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	2.3% 1/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Gastrointestinal disorders Abdominal discomfort	4.5% 4/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	2.3% 1/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Gastrointestinal disorders Dental caries	2.3% 2/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	2.3% 1/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Gastrointestinal disorders Faeces soft	2.3% 2/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	2.3% 1/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Gastrointestinal disorders Toothache	3.4% 3/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	0.00% 0/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Infections and infestations Nasopharyngitis	21.6% 19/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	20.9% 9/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Infections and infestations Upper respiratory tract infection	20.5% 18/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	11.6% 5/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Infections and infestations Ear infection	8.0% 7/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	11.6% 5/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Infections and infestations Influenza	11.4% 10/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	4.7% 2/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Infections and infestations Pharyngitis streptococcal	4.5% 4/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	9.3% 4/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Infections and infestations Gastroenteritis	3.4% 3/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	4.7% 2/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Infections and infestations Gastroenteritis viral	3.4% 3/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	4.7% 2/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Infections and infestations Lower respiratory tract infection	2.3% 2/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	4.7% 2/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Infections and infestations Conjunctivitis	2.3% 2/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	2.3% 1/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Infections and infestations Impetigo	3.4% 3/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	0.00% 0/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Infections and infestations Tonsillitis	3.4% 3/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	0.00% 0/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Respiratory, thoracic and mediastinal disorders Cough	14.8% 13/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	25.6% 11/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	3.4% 3/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	11.6% 5/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.8% 6/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	2.3% 1/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.5% 4/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	2.3% 1/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Respiratory, thoracic and mediastinal disorders Sinus congestion	3.4% 3/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	0.00% 0/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
General disorders Pyrexia	19.3% 17/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	20.9% 9/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
General disorders Fatigue	6.8% 6/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	0.00% 0/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
General disorders Influenza like illness	0.00% 0/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	11.6% 5/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
General disorders Non-cardiac chest pain	3.4% 3/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	0.00% 0/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Injury, poisoning and procedural complications Fall	15.9% 14/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	9.3% 4/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Injury, poisoning and procedural complications Contusion	6.8% 6/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	4.7% 2/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Injury, poisoning and procedural complications Ligament sprain	3.4% 3/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	2.3% 1/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Injury, poisoning and procedural complications Arthropod bite	2.3% 2/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	2.3% 1/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Skin and subcutaneous tissue disorders Rash	22.7% 20/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	4.7% 2/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Musculoskeletal and connective tissue disorders Muscle spasms	11.4% 10/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	2.3% 1/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Musculoskeletal and connective tissue disorders Pain in extremity	6.8% 6/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	11.6% 5/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Musculoskeletal and connective tissue disorders Back pain	1.1% 1/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	4.7% 2/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Nervous system disorders Headache	13.6% 12/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	18.6% 8/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Nervous system disorders Dizziness	3.4% 3/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	2.3% 1/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Psychiatric disorders Attention deficit hyperactivity disorder	2.3% 2/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	2.3% 1/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Investigations Weight increased	1.1% 1/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	4.7% 2/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Metabolism and nutrition disorders Decreased appetite	6.8% 6/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	4.7% 2/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Renal and urinary disorders Chromaturia	2.3% 2/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	4.7% 2/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Renal and urinary disorders Pollakiuria	3.4% 3/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	0.00% 0/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
Ear and labyrinth disorders Ear pain	3.4% 3/88 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.	0.00% 0/43 • Up to Week 52 Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.