ACT DMD: Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)

• Sponsor: PTC Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01826487
• Collaborator: (none)
• Enrollment: 230
• Locations: 55
• Arms: 2
• Actual Duration (Months): 28.8
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Dystrophinopathy is a disease continuum that includes Duchenne muscular dystrophy, which develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. Loss of dystrophin causes muscle fragility that leads to weakness and loss of walking ability. A specific type of mutation, called a nonsense (premature stop codon) mutation is the cause of dystrophinopathy in approximately 10-15 percent (%) of boys with the disease. Ataluren is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. The main goal of this Phase 3 study is to evaluate the effect of ataluren on walking ability. The effect of ataluren on physical function, quality of life, and activities of daily living will be evaluated. This study will also provide additional information on the long-term safety of ataluren.

Condition or Disease	Intervention/Treatment	Phase
Muscular Dystrophy, Duchenne; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn	Drug: Ataluren; Drug: Placebo	Phase 3

Detailed Description

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to determine the efficacy and safety of ataluren in participants with nmDMD.

Study Design

• Study Type: Interventional
• Actual Enrollment: 230 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Efficacy and Safety Study of Ataluren in Patients With Nonsense Mutation Dystrophinopathy
• Actual Study Start Date: Mar 26, 2013
• Actual Primary Completion Date: Aug 20, 2015
• Actual Study Completion Date: Aug 20, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants will receive placebo matching to ataluren orally 3 times a day (TID) at morning, midday, and evening for 48 weeks.	Drug: Placebo; Placebo will be administered as per the schedule specified in the arm.
Experimental: Ataluren Participants will receive ataluren suspension orally TID, 10 milligrams/kilogram (mg/kg) at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Drug: Ataluren; Ataluren will be administered as per the dose and schedule specified in the arm.; Other Names: PTC124

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in 6MWD at Week 48 [Baseline, Week 48]

   The 6MWD test is a non-encouraged test performed in a 30 meters long flat corridor, where the participant is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures by measuring the 6MWD in meters. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test. Participants with confirmed loss of ambulation at a particular visit were assigned a 6MWD result of 0. Baseline and Week 48 6MWD values are each the average of two valid 6MWD values, or a single available value if one was missing.

Secondary Outcome Measures

1. Time to 10 Percent (%) Persistent Worsening in 6MWD [Baseline to Week 48]

   The 6MWD test is a non-encouraged test performed in a 30 meters long flat corridor, where the participant is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures by measuring the 6MWD in meters. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test. Time to 10% persistent worsening in 6MWD was defined as the last time that 6MWD was not 10% worse compared with baseline. Time to 10% persistent worsening in 6MWD <300 meters, >=300 to 400 meters, and >=400 meters was evaluated. For participants who did not have 10% 6MWD worsening or who were removed from study, time to 10% 6MWD worsening was censored at the time of the last 6MWD test. Participants who became non-ambulatory were considered to have 10% worsening.

2. Change From Baseline in Time to Walk/Run 10 Meters at Week 48 [Baseline, Week 48]

   During the test for walking/running 10 meters, the method of walk/run used by the participant was categorized as follows: 1. Unable to walk independently; 2. Unable to walk independently but can walk with support from a person or with assistive device (full leg calipers [knee-ankle-foot orthoses ] or walker); 3. Highly adapted gait, 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 (that is, cannot achieve both feet off the ground); 6. Runs and gets both feet off the ground (with no double stance phase). If the time taken to perform a test exceeded 30 seconds or if a participant could not perform the test due to disease progression, a value of 30 seconds was used. A cumulative change from baseline data has been reported.

3. Change From Baseline in Time to Climb 4 Stairs at Week 48 [Baseline, Week 48]

   During the test for stair-climbing, the method of climbing used by the participant was categorized as follows: 1. Unable to up climb 4 standard stairs; 2. Climbs 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), using both arms on one or both handrails; 3. Climbs 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), using one arm on one handrail; 4. Climbs 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), not needing handrail; 5. Climbs 4 standard stairs alternating feet, needs handrail for support; 6. Climbs 4 standard stairs alternating feet, not needing handrail support. A cumulative change from baseline data has been reported.

4. Change From Baseline in Time to Descend 4 Stairs at Week 48 [Baseline, Week 48]

   During the test for stair-descending, the method of descending used by the participant was categorized as follows: 1. Unable to descend 4 standard stairs; 2. Descends 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), using both arms on one or both handrails; 3. Descends 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), using one arm on one handrail; 4. Descends 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), not needing handrail; 5. Descends 4 standard stairs alternating feet, needs handrail for support; 6. Descends 4 standard stairs alternating feet, not needing handrail support. A cumulative change from baseline data has been reported.

5. Percentage of Participants With Treatment-Emergent Adverse Events (AEs) [Baseline up to Week 54]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. Treatment-emergent adverse event (TEAE) was defined as an adverse event that occurred or worsened in the period extending from first dose of study drug to 6 weeks after the last dose of study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

Other Outcome Measures

1. Change From Baseline in Physical Function Total Score as Measured by NSAA at Week 48 [Baseline, Week 48]

   Physical function was assessed via the NSAA, a functional scale specifically designed for ambulant Duchenne muscular dystrophy (DMD) participants. The assessment comprised tests for 17 abilities of a participant, such as ability to stand, rise from the floor, get from lying to sitting, get from sitting to standing, raise one's head, stand on one's heels, hop, jump, and run. For each activity, a score of 0, 1, or 2 was recorded, with 0 = "unable to achieve independently," 1 = "modified method but achieves goal independent of physical assistance from another," or 2 = "normal- achieves goal without any assistance." The sum of these scores (except for 'raise one's head' activity score) was reported as the ordinal total score, which was transformed to a linear total score ranging from 0 (worst) to 100 (best). Participants with confirmed loss of ambulation at a particular visit were assigned a score of 0.

2. Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel [Baseline, Week 48]

   Changes in activities of daily living and disease symptoms were captured via a DMD-specific survey administered by Site personnel. At screening or baseline, the participant and/or parent/caregiver were asked to identify any activities of daily living (for example, ambulation, balance, personal hygiene/grooming, dressing and undressing, self-feeding, using the bathroom, handwriting, school performance, behavior or energy level) or symptoms that were affected by the participant's DMD. At post-baseline visit (Week 48), the same participant and/or parent/caregiver was asked to describe any changes from baseline in those activities of daily living/symptoms, within the following categories: physical functioning; general energy level; cognition/school function; emotional/social functioning; and sleep. Changes from baseline were reported on a 5-point Likert scale: 1 (much worse), 2 (slightly worse), 3 (unchanged), 4 (slightly better), or 5 (much better).

3. Change From Baseline in PODCI Transfers/Basic Mobility and Sports/Physical Functioning Scores at Week 48 [Baseline, Week 48]

   Changes in health-related quality of life (HRQL) were measured via the PODCI questionnaire that has been shown to correlate with disease progression and clinical outcome measures in DMD. PODCI includes a Global Functioning Scale and 5 core scales: Upper Extremity and Physical Function,Transfer/Basic Mobility, Sports/Physical Functioning, Pain/Comfort,and Happiness. The following PODCI domains were prespecified in the protocol for analysis:Transfers/Basic Mobility domain assesses difficulty experienced in performing routine motor activities in daily life. Sports/Physical Functioning domain assesses difficulty encountered in participating in more active recreational activities. Each domain was scored from 0 to 100, with 0 representing a poor outcome/worse health, while 100 representing the highest level of functioning and least pain.

4. Ataluren Plasma Concentration [Weeks 8, 16, 24, 32, 40, and 48]

   Plasma samples for the determination of ataluren concentrations were analyzed using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC/MS-MS) method with a lower limit of quantitation of 0.5 micrograms/milliliter (mcg/mL).

5. Study Drug Compliance [Baseline to Week 48]

   Study drug compliance was assessed by quantification of used and unused study drug. Compliance was assessed in terms of the percentage of drug actually taken relative to the amount that should have been taken during the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 16 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ability to provide written informed consent (parental/guardian consent if applicable)/assent per local requirements.

• Phenotypic evidence of dystrophinopathy based on the onset of characteristic clinical symptoms or signs (for example; proximal muscle weakness, waddling gait, and Gowers' maneuver) by 6 years of age, an elevated serum creatinine kinase level, and ongoing difficulty with walking.

• Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing from a laboratory certified by the College of American Pathologists (CAP), the Clinical Laboratory Improvement Act/Amendment (CLIA) or an equivalent organization.

• Documentation that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the dystrophin gene.

• Use of systemic corticosteroids (prednisone, prednisolone, or deflazacort) for a minimum of 6 months immediately prior to start of study treatment, with no significant change in dosage or dosing regimen (not related to body weight change) for a minimum of 3 months immediately prior to start of study treatment and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study.

• Valid Screening 6-minute walk distance (6MWD) greater than or equal to (≥) 150 meters. Valid Screening 6MWD must have been less than or equal to (≤) 80% of predicted for age and height.

• Results of the 2 Baseline 6MWD results must be determined as valid and results of the Day 2 Baseline 6MWD must be within 20% of the Day 1 Baseline 6MWD.

• Baseline 6MWD (mean of valid Day 1 and Day 2 values) must be no more than a 20% change from the valid Screening 6MWD.

• Confirmed screening laboratory values within the central laboratory ranges (hepatic, renal, and serum electrolyte parameters).

• Willingness to abstain from sexual intercourse or employ an approved method of contraception during the period of study drug administration and 6-week follow-up period.

• Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.

Exclusion Criteria:

• Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment.

• Initiation of systemic corticosteroids therapy within 6 months prior to start of study treatment.

• Change in systemic corticosteroid therapy (for example; change in type of drug, dose modification not related to body weight change, schedule modification, interruption, or reinitiation) within 3 months prior to start of study treatment.

• Any change (initiation, change in type of drug, dose modification, schedule modification,interruption, discontinuation, or reinitiation) in prophylaxis/treatment for congestive heart failure (CHF) within 3 months prior to start of study treatment.

• Ongoing use of coumarin-based anticoagulants (for example; warfarin), phenytoin, tolbutamide, or paclitaxel.

• Prior therapy with ataluren.

• Known hypersensitivity to any of the ingredients or excipients of the study drug.

• Exposure to another investigational drug within 3 months prior to start of study treatment.

• History of major surgical procedure within 6 weeks prior to start of study treatment.

• Ongoing immunosuppressive therapy (other than corticosteroids).

• Ongoing participation in any clinical trial (except for studies specifically approved by PTC Therapeutics).

• Expectation of major surgical procedure (for example; scoliosis surgery) during the 12-month treatment period of the study.

• Requirement for daytime ventilator assistance.

• Uncontrolled clinical symptoms and signs of CHF (American College of Cardiology/American Heart Association Stage C or Stage D).

• Prior or ongoing medical condition (for example; concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings (for example; lower limb injury that may affect 6MWT performance), electrocardiogram (ECG) findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles	Los Angeles	California	United States	90095
2	UC Davis Medical Center	Sacramento	California	United States	95817
3	Children's Hospital Colorado - Center for Cancer and Blood Disorders	Aurora	Colorado	United States	80045
4	Child Neurology Center of Northwest Florida	Gulf Breeze	Florida	United States	32561
5	Rush University Medical Center	Chicago	Illinois	United States	60612
6	University of Iowa	Iowa City	Iowa	United States	52242
7	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
8	Boston Children's Hospital	Boston	Massachusetts	United States	02115
9	Children's Hospital Boston	Boston	Massachusetts	United States	02115
10	University of Minnesota	Minneapolis	Minnesota	United States	55455
11	Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research	Saint Louis	Missouri	United States	63110
12	Columbia University College of Physicians & Surgeons	New York	New York	United States	10032
13	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
14	Nationwide Children's Hospital	Columbus	Ohio	United States	43209
15	Oregon Health & Science University	Portland	Oregon	United States	97239
16	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
17	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
18	Childrens Medical Center Dallas, Texas	Dallas	Texas	United States	75207
19	Texas Children's Hospital	Houston	Texas	United States	77030
20	University of Utah	Salt Lake City	Utah	United States	84112
21	Seattle Children's Hospital - Childhood Cancer and Blood Disorders	Seattle	Washington	United States	98105
22	The Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
23	The Royal Children's Hospital	Parkville	Victoria	Australia	3052
24	UZ Leuven	Leuven		Belgium	3000
25	Universidade Federal do Rio de Janeiro - Instituto de Puericultura e Pediatria Martagao Gesteira	Rio de Janeiro		Brazil	21.941-912
26	Sao Paulo University -HC/FMUSP	São Paulo		Brazil	05403-900
27	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B 6A8
28	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
29	Children's Hospital of Western Ontario	London	Ontario	Canada	N6A 2E3
30	Hospital Luis Calvo Mackenna	Santiago	Región Metropolitana	Chile
31	Hospital Clinico Universidad Catolica	Santiago		Chile	8330073
32	University Hospital Brno	Brno		Czechia	635 00
33	Motol University Hospital	Praha		Czechia	150 06
34	Hospital de la Timone	Marseille		France	13385
35	CHU de Nantes	Nantes Cedex		France	44093
36	Hopital Necker - Enfants Malades	Paris		France	75015
37	Groupe Hospitalier La Pitie-Salpetriere	Paris		France	75651
38	University of Essen-Duisburg	Essen		Germany	45122
39	University Hospital Medical Center Freiburg	Freiburg		Germany	79106
40	Hadassah University Hospital	Jerusalem		Israel	91240
41	Policlinico Universitario G. Martino	Messina	Sicily	Italy	98125
42	Fondazione IRCS Ca Granda Ospedale Maggiore Policlinico di Milano	Milan		Italy	20122
43	Bambino Gesu Hospital	Rome		Italy	00165
44	U.O. Complessa di Neuropsichiatria Infantile	Rome		Italy	00168
45	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
46	Medical University of Warsaw	Warsaw		Poland	85- 822
47	Hospital Sant Joan de Deu	Barcelona		Spain	08950
48	Hospital Universitari i Politecnic la Fe	Valencia		Spain	46026
49	Queen Silvia Children's Hospital	Goteburg		Sweden	SE-416 85
50	Astrid Lindgren Childrens Hospital	Stockholm		Sweden	17176
51	CHUV Lausanne	Lausanne		Switzerland	1011
52	Hacettepe Childrens Hospital	Ankara		Turkey	06100
53	University College London Institute of Child Health	London		United Kingdom	WC1N 1EH
54	Royal Manchester Children's Hospital	Manchester		United Kingdom	M13 9WL
55	The Newcastle upon Tyne Hospitals, NHS Foundation Trust	Newcastle upon Tyne		United Kingdom	NE1 3BZ

Sponsors and Collaborators

• PTC Therapeutics

Investigators

• Study Director: Robert Spiegel, M.D., PTC Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: PTC Therapeutics
• ClinicalTrials.gov Identifier: NCT01826487
• Other Study ID Numbers: PTC124-GD-020-DMD; 2012-004527-20
• First Posted: Apr 8, 2013
• Last Update Posted: Aug 4, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by PTC Therapeutics: Duchenne muscular dystrophy; Dystrophinopathy; Nonsense mutation; Premature stop codon; Becker muscular dystrophy; DMD/BMD; PTC124; Ataluren
• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne; Musculoskeletal Diseases; Muscular Diseases; Muscular Disorders, Atrophic; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked

Study Results

Participant Flow

Recruitment Details	A total of 291 participants were screened for eligibility, of which 61 participants did not meet entry criteria.
Pre-assignment Detail	A total of 230 eligible participants were randomized in 1:1 ratio to receive either placebo or ataluren. 2 participants, 1 in each treatment arm, were excluded from intent-to-treat (ITT) population; as they did not have at least 1 valid post-baseline 6-minute walk distance (6MWD) value, a requirement for inclusion in ITT population.

Arm/Group Title	Placebo	Ataluren
Arm/Group Description	Participants received placebo matched to ataluren orally 3 times a day (TID) at morning, midday, and evening for 48 weeks.	Participants received ataluren suspension orally TID, 10 milligrams/kilogram (mg/kg) at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
Period Title: Overall Study
STARTED	115	115
As-treated Population	115	115
ITT Population	114	114
COMPLETED	111	110
NOT COMPLETED	4	5

Baseline Characteristics

Arm/Group Title	Placebo	Ataluren	Total
Arm/Group Description	Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Total of all reporting groups
Overall Participants	115	115	230
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.0 (1.65)	8.9 (1.79)	8.9 (1.72)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	115 100%	115 100%	230 100%
6 Minute Walk Distance (6MWD) (meters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meters]	362.69 (81.424)	364.04 (73.342)	363.36 (77.322)
Time to Walk/Run 10 Meters (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	6.83 (2.924)	6.66 (3.078)	6.75 (2.996)
Time to Climb 4 Stairs (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	6.76 (7.287)	5.99 (5.347)	6.38 (6.389)
Time to Descend 4 Stairs (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	5.05 (5.362)	5.07 (5.157)	5.06 (5.247)
Physical Function Total Score as Measured by North Star Ambulatory Assessment (NSAA) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	60.2 (18.37)	60.9 (17.97)	60.6 (18.14)
Baseline 6MWT (Count of Participants)
<300 meters	22 19.1%	25 21.7%	47 20.4%
>=300 to <400 meters	52 45.2%	47 40.9%	99 43%
>=400 meters	41 35.7%	43 37.4%	84 36.5%
Pediatric Outcomes Data Collection Instrument (PODCI) Scores (units on a scale) [Mean (Standard Deviation) ]
Transfers/Basic Mobility Score	81.4 (15.79)	83.9 (13.10)	82.7 (14.53)
Sports/Physical Functioning Score	56.0 (20.94)	56.2 (18.94)	56.1 (19.92)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in 6MWD at Week 48
Description	The 6MWD test is a non-encouraged test performed in a 30 meters long flat corridor, where the participant is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures by measuring the 6MWD in meters. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test. Participants with confirmed loss of ambulation at a particular visit were assigned a 6MWD result of 0. Baseline and Week 48 6MWD values are each the average of two valid 6MWD values, or a single available value if one was missing.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Multiple imputation was applied to impute missing values within the treatment groups.

Arm/Group Title	Placebo	Ataluren
Arm/Group Description	Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
Measure Participants	114	114
Least Squares Mean (Standard Error) [meters]	-60.67 (9.323)	-47.69 (9.247)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ataluren
	Comments	Analysis was performed using analysis of covariance (ANCOVA) method including stratification factors for age (less than [<] 9 years versus [vs.] greater than or equal to [>=] 9 years), duration of use of corticosteroids at baseline (approx. >=6 to <12 months vs. >=12 months), and baseline 6MWD category (>=350 meters vs <350 meters), as well as baseline 6MWD as covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.213
	Comments	Threshold for significance at 0.05. Secondary endpoints were tested for significance, only if the primary endpoint was statistically significant.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	12.98
	Confidence Interval	(2-Sided) 95%; -7.44 to 33.39
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.415
	Estimation Comments

2. Secondary Outcome

Title	Time to 10 Percent (%) Persistent Worsening in 6MWD
Description	The 6MWD test is a non-encouraged test performed in a 30 meters long flat corridor, where the participant is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures by measuring the 6MWD in meters. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test. Time to 10% persistent worsening in 6MWD was defined as the last time that 6MWD was not 10% worse compared with baseline. Time to 10% persistent worsening in 6MWD <300 meters, >=300 to 400 meters, and >=400 meters was evaluated. For participants who did not have 10% 6MWD worsening or who were removed from study, time to 10% 6MWD worsening was censored at the time of the last 6MWD test. Participants who became non-ambulatory were considered to have 10% worsening.
Time Frame	Baseline to Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Multiple imputation was applied to impute missing values within treatment groups. Here, 'Number analyzed 'signifies participants evaluable for specified categories.

Arm/Group Title	Placebo	Ataluren
Arm/Group Description	Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
Measure Participants	114	114
<300 meters	56	164
>=300 to <400 meters	280	NA
>=400 meters	NA	NA

3. Secondary Outcome

Title	Change From Baseline in Time to Walk/Run 10 Meters at Week 48
Description	During the test for walking/running 10 meters, the method of walk/run used by the participant was categorized as follows: 1. Unable to walk independently; 2. Unable to walk independently but can walk with support from a person or with assistive device (full leg calipers [knee-ankle-foot orthoses ] or walker); 3. Highly adapted gait, 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 (that is, cannot achieve both feet off the ground); 6. Runs and gets both feet off the ground (with no double stance phase). If the time taken to perform a test exceeded 30 seconds or if a participant could not perform the test due to disease progression, a value of 30 seconds was used. A cumulative change from baseline data has been reported.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Ataluren
Arm/Group Description	Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
Measure Participants	110	109
Mean (Standard Deviation) [seconds]	3.47 (6.393)	2.27 (5.216)

4. Secondary Outcome

Title	Change From Baseline in Time to Climb 4 Stairs at Week 48
Description	During the test for stair-climbing, the method of climbing used by the participant was categorized as follows: 1. Unable to up climb 4 standard stairs; 2. Climbs 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), using both arms on one or both handrails; 3. Climbs 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), using one arm on one handrail; 4. Climbs 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), not needing handrail; 5. Climbs 4 standard stairs alternating feet, needs handrail for support; 6. Climbs 4 standard stairs alternating feet, not needing handrail support. A cumulative change from baseline data has been reported.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Ataluren
Arm/Group Description	Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
Measure Participants	103	105
Mean (Standard Deviation) [seconds]	4.46 (7.310)	2.65 (5.297)

5. Secondary Outcome

Title	Change From Baseline in Time to Descend 4 Stairs at Week 48
Description	During the test for stair-descending, the method of descending used by the participant was categorized as follows: 1. Unable to descend 4 standard stairs; 2. Descends 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), using both arms on one or both handrails; 3. Descends 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), using one arm on one handrail; 4. Descends 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), not needing handrail; 5. Descends 4 standard stairs alternating feet, needs handrail for support; 6. Descends 4 standard stairs alternating feet, not needing handrail support. A cumulative change from baseline data has been reported.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Ataluren
Arm/Group Description	Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
Measure Participants	100	106
Mean (Standard Deviation) [seconds]	3.97 (7.854)	2.15 (5.306)

6. Other Pre-specified Outcome

Title	Change From Baseline in Physical Function Total Score as Measured by NSAA at Week 48
Description	Physical function was assessed via the NSAA, a functional scale specifically designed for ambulant Duchenne muscular dystrophy (DMD) participants. The assessment comprised tests for 17 abilities of a participant, such as ability to stand, rise from the floor, get from lying to sitting, get from sitting to standing, raise one's head, stand on one's heels, hop, jump, and run. For each activity, a score of 0, 1, or 2 was recorded, with 0 = "unable to achieve independently," 1 = "modified method but achieves goal independent of physical assistance from another," or 2 = "normal- achieves goal without any assistance." The sum of these scores (except for 'raise one's head' activity score) was reported as the ordinal total score, which was transformed to a linear total score ranging from 0 (worst) to 100 (best). Participants with confirmed loss of ambulation at a particular visit were assigned a score of 0.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Ataluren
Arm/Group Description	Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
Measure Participants	108	106
Mean (Standard Deviation) [units on a scale]	-8.4 (10.65)	-6.3 (10.64)

7. Other Pre-specified Outcome

Title	Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel
Description	Changes in activities of daily living and disease symptoms were captured via a DMD-specific survey administered by Site personnel. At screening or baseline, the participant and/or parent/caregiver were asked to identify any activities of daily living (for example, ambulation, balance, personal hygiene/grooming, dressing and undressing, self-feeding, using the bathroom, handwriting, school performance, behavior or energy level) or symptoms that were affected by the participant's DMD. At post-baseline visit (Week 48), the same participant and/or parent/caregiver was asked to describe any changes from baseline in those activities of daily living/symptoms, within the following categories: physical functioning; general energy level; cognition/school function; emotional/social functioning; and sleep. Changes from baseline were reported on a 5-point Likert scale: 1 (much worse), 2 (slightly worse), 3 (unchanged), 4 (slightly better), or 5 (much better).
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed 'signifies participants evaluable for specified categories.

Arm/Group Title	Placebo	Ataluren
Arm/Group Description	Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
Measure Participants	114	114
Much better	1 0.9%	4 3.5%
Slightly better	7 6.1%	7 6.1%
Unchanged	67 58.3%	73 63.5%
Slightly worse	6 5.2%	2 1.7%
Much worse	1 0.9%	2 1.7%
Much better	5 4.3%	8 7%
Slightly better	13 11.3%	16 13.9%
Unchanged	57 49.6%	60 52.2%
Slightly worse	19 16.5%	21 18.3%
Much worse	18 15.7%	3 2.6%
Much better	4 3.5%	4 3.5%
Slightly better	8 7%	13 11.3%
Unchanged	61 53%	65 56.5%
Slightly worse	17 14.8%	15 13%
Much worse	15 13%	13 11.3%
Much better	4 3.5%	5 4.3%
Slightly better	9 7.8%	10 8.7%
Unchanged	38 33%	44 38.3%
Slightly worse	7 6.1%	8 7%
Much worse	7 6.1%	1 0.9%
Much better	6 5.2%	5 4.3%
Slightly better	12 10.4%	20 17.4%
Unchanged	71 61.7%	74 64.3%
Slightly worse	3 2.6%	3 2.6%
Much worse	0 0%	2 1.7%
Much better	3 2.6%	8 7%
Slightly better	9 7.8%	21 18.3%
Unchanged	75 65.2%	68 59.1%
Slightly worse	5 4.3%	6 5.2%
Much worse	2 1.7%	2 1.7%
Much better	3 2.6%	8 7%
Slightly better	12 10.4%	12 10.4%
Unchanged	54 47%	63 54.8%
Slightly worse	11 9.6%	5 4.3%
Much worse	3 2.6%	1 0.9%
Much better	3 2.6%	3 2.6%
Slightly better	4 3.5%	8 7%
Unchanged	73 63.5%	76 66.1%
Slightly worse	5 4.3%	2 1.7%
Much worse	0 0%	2 1.7%
Much better	0 0%	1 0.9%
Slightly better	5 4.3%	6 5.2%
Unchanged	15 13%	13 11.3%
Slightly worse	2 1.7%	3 2.6%
Much worse	1 0.9%	0 0%

8. Other Pre-specified Outcome

Title	Change From Baseline in PODCI Transfers/Basic Mobility and Sports/Physical Functioning Scores at Week 48
Description	Changes in health-related quality of life (HRQL) were measured via the PODCI questionnaire that has been shown to correlate with disease progression and clinical outcome measures in DMD. PODCI includes a Global Functioning Scale and 5 core scales: Upper Extremity and Physical Function,Transfer/Basic Mobility, Sports/Physical Functioning, Pain/Comfort,and Happiness. The following PODCI domains were prespecified in the protocol for analysis:Transfers/Basic Mobility domain assesses difficulty experienced in performing routine motor activities in daily life. Sports/Physical Functioning domain assesses difficulty encountered in participating in more active recreational activities. Each domain was scored from 0 to 100, with 0 representing a poor outcome/worse health, while 100 representing the highest level of functioning and least pain.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Ataluren
Arm/Group Description	Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
Measure Participants	110	109
Transfers/Basic Mobility Score	-8.8 (15.80)	-6.6 (14.76)
Sports/Physical Functioning Score	-7.3 (15.87)	-5.6 (15.91)

9. Other Pre-specified Outcome

Title	Ataluren Plasma Concentration
Description	Plasma samples for the determination of ataluren concentrations were analyzed using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC/MS-MS) method with a lower limit of quantitation of 0.5 micrograms/milliliter (mcg/mL).
Time Frame	Weeks 8, 16, 24, 32, 40, and 48

Outcome Measure Data

Analysis Population Description

As-treated population included all randomized participants who actually received any study treatment. Here, 'Number analyzed 'signifies participants evaluable at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
Measure Participants	115
Week 08	4.230 (5.3913)
Week 16	3.429 (3.9275)
Week 24	3.323 (3.6135)
Week 32	3.480 (3.1053)
Week 40	3.997 (4.7615)
Week 48	3.544 (3.8082)

10. Other Pre-specified Outcome

Title	Study Drug Compliance
Description	Study drug compliance was assessed by quantification of used and unused study drug. Compliance was assessed in terms of the percentage of drug actually taken relative to the amount that should have been taken during the study.
Time Frame	Baseline to Week 48

Outcome Measure Data

Analysis Population Description

As-treated population included all randomized participants who actually received any study treatment.

Arm/Group Title	Placebo	Ataluren
Arm/Group Description	Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
Measure Participants	115	115
Mean (Standard Deviation) [percentage of drug]	95.1 (9.43)	95.7 (7.57)

11. Secondary Outcome

Title	Percentage of Participants With Treatment-Emergent Adverse Events (AEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. Treatment-emergent adverse event (TEAE) was defined as an adverse event that occurred or worsened in the period extending from first dose of study drug to 6 weeks after the last dose of study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.
Time Frame	Baseline up to Week 54

Outcome Measure Data

Analysis Population Description

As-treated population included all randomized participants who actually received any study treatment.

Arm/Group Title	Placebo	Ataluren
Arm/Group Description	Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
Measure Participants	115	115
Number [percentage of participants]	87.8 76.3%	89.6 77.9%

Adverse Events

Time Frame	Baseline up to 6 weeks after the last dose of study drug (Week 54)
Adverse Event Reporting Description	As-treated population included all randomized participants who actually received any study treatment.
Arm/Group Title	Placebo		Ataluren
Arm/Group Description	Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.		Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
All Cause Mortality
	Placebo		Ataluren
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Ataluren
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/115 (3.5%)		4/115 (3.5%)
Cardiac disorders
Myocarditis	0/115 (0%)	0	1/115 (0.9%)	1
Hepatobiliary disorders
Hepatic function abnormal	0/115 (0%)	0	1/115 (0.9%)	1
Infections and infestations
Pneumonia	2/115 (1.7%)	2	0/115 (0%)	0
Bronchiolitis	1/115 (0.9%)	1	0/115 (0%)	0
Gastroenteritis	0/115 (0%)	0	1/115 (0.9%)	1
Injury, poisoning and procedural complications
Post-traumatic pain	1/115 (0.9%)	1	0/115 (0%)	0
Femur fracture	0/115 (0%)	0	1/115 (0.9%)	1
Lower limb fracture	0/115 (0%)	0	1/115 (0.9%)	1
Musculoskeletal and connective tissue disorders
Tendon disorder	1/115 (0.9%)	1	0/115 (0%)	0
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy	1/115 (0.9%)	1	0/115 (0%)	0
Nasal turbinate hypertrophy	1/115 (0.9%)	1	0/115 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Ataluren
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	99/115 (86.1%)		103/115 (89.6%)
Blood and lymphatic system disorders
Neutropenia	0/115 (0%)		1/115 (0.9%)
Splenomegaly	0/115 (0%)		1/115 (0.9%)
Leukocytosis	1/115 (0.9%)		0/115 (0%)
Lymphadenopathy	1/115 (0.9%)		0/115 (0%)
Cardiac disorders
Right ventricular hypertrophy	0/115 (0%)		2/115 (1.7%)
Left ventricular dysfunction	0/115 (0%)		1/115 (0.9%)
Left ventricular hypertrophy	0/115 (0%)		1/115 (0.9%)
Myocardial fibrosis	0/115 (0%)		1/115 (0.9%)
Palpitations	2/115 (1.7%)		1/115 (0.9%)
Cardiomyopathy	1/115 (0.9%)		0/115 (0%)
Wolff-Parkinson-White syndrome	1/115 (0.9%)		0/115 (0%)
Ear and labyrinth disorders
Ear pain	4/115 (3.5%)		0/115 (0%)
Middle ear effusion	1/115 (0.9%)		0/115 (0%)
Tympanic membrane disorder	1/115 (0.9%)		0/115 (0%)
Endocrine disorders
Hypothyroidism	0/115 (0%)		1/115 (0.9%)
Hyperaldosteronism	1/115 (0.9%)		0/115 (0%)
Eye disorders
Astigmatism	0/115 (0%)		1/115 (0.9%)
Cataract	1/115 (0.9%)		1/115 (0.9%)
Conjunctivitis	2/115 (1.7%)		0/115 (0%)
Eye allergy	0/115 (0%)		1/115 (0.9%)
Conjunctivitis allergic	1/115 (0.9%)		0/115 (0%)
Eye movement disorder	1/115 (0.9%)		0/115 (0%)
Eyelid oedema	1/115 (0.9%)		0/115 (0%)
Myopia	1/115 (0.9%)		0/115 (0%)
Gastrointestinal disorders
Diarrhoea	10/115 (8.7%)		20/115 (17.4%)
Abdominal pain upper	13/115 (11.3%)		9/115 (7.8%)
Abdominal pain	5/115 (4.3%)		7/115 (6.1%)
Abdominal discomfort	0/115 (0%)		3/115 (2.6%)
Constipation	10/115 (8.7%)		3/115 (2.6%)
Flatulence	1/115 (0.9%)		2/115 (1.7%)
Abnormal faeces	0/115 (0%)		1/115 (0.9%)
Breath odour	0/115 (0%)		1/115 (0.9%)
Dental caries	0/115 (0%)		1/115 (0.9%)
Dry mouth	1/115 (0.9%)		1/115 (0.9%)
Dyspepsia	3/115 (2.6%)		1/115 (0.9%)
Gastritis	1/115 (0.9%)		1/115 (0.9%)
Gastrooesophageal reflux disease	2/115 (1.7%)		1/115 (0.9%)
Haemorrhoids	1/115 (0.9%)		1/115 (0.9%)
Anal fissure	1/115 (0.9%)		0/115 (0%)
Food poisoning	1/115 (0.9%)		0/115 (0%)
Haematochezia	1/115 (0.9%)		0/115 (0%)
Inguinal hernia	1/115 (0.9%)		0/115 (0%)
Irritable bowel syndrome	1/115 (0.9%)		0/115 (0%)
Vomiting	21/115 (18.3%)		26/115 (22.6%)
Nausea	7/115 (6.1%)		7/115 (6.1%)
Tooth crowding	0/115 (0%)		2/115 (1.7%)
Malocclusion	0/115 (0%)		1/115 (0.9%)
Odynophagia	0/115 (0%)		1/115 (0.9%)
Oral pain	0/115 (0%)		1/115 (0.9%)
Rectal haemorrhage	2/115 (1.7%)		0/115 (0%)
Swollen tongue	1/115 (0.9%)		0/115 (0%)
Toothache	1/115 (0.9%)		0/115 (0%)
General disorders
Pyrexia	12/115 (10.4%)		16/115 (13.9%)
Disease progression	14/115 (12.2%)		9/115 (7.8%)
Abasia	0/115 (0%)		3/115 (2.6%)
Oedema peripheral	0/115 (0%)		3/115 (2.6%)
Fatigue	3/115 (2.6%)		1/115 (0.9%)
Non-cardiac chest pain	1/115 (0.9%)		1/115 (0.9%)
Influenza like illness	2/115 (1.7%)		1/115 (0.9%)
Gait disturbance	1/115 (0.9%)		0/115 (0%)
Malaise	3/115 (2.6%)		0/115 (0%)
Thirst	1/115 (0.9%)		0/115 (0%)
Hepatobiliary disorders
Hepatic function abnormal	1/115 (0.9%)		0/115 (0%)
Hepatic steatosis	1/115 (0.9%)		0/115 (0%)
Immune system disorders
Allergy to chemicals	0/115 (0%)		1/115 (0.9%)
Seasonal allergy	2/115 (1.7%)		2/115 (1.7%)
Rhinitis allergic	0/115 (0%)		1/115 (0.9%)
Allergy to vaccine	1/115 (0.9%)		0/115 (0%)
Drug hypersensitivity	2/115 (1.7%)		0/115 (0%)
Infections and infestations
Ear infection	1/115 (0.9%)		6/115 (5.2%)
Gastroenteritis	4/115 (3.5%)		5/115 (4.3%)
Influenza	5/115 (4.3%)		3/115 (2.6%)
Bronchitis	3/115 (2.6%)		2/115 (1.7%)
Conjunctivitis infective	0/115 (0%)		2/115 (1.7%)
Fungal skin infection	1/115 (0.9%)		2/115 (1.7%)
Gastroenteritis viral	0/115 (0%)		2/115 (1.7%)
Gastrointestinal viral infection	0/115 (0%)		2/115 (1.7%)
Hordeolum	3/115 (2.6%)		2/115 (1.7%)
Eye infection	1/115 (0.9%)		1/115 (0.9%)
Gingivitis	0/115 (0%)		1/115 (0.9%)
Herpes simplex	0/115 (0%)		1/115 (0.9%)
Lower respiratory tract infection	4/115 (3.5%)		1/115 (0.9%)
Lung infection	0/115 (0%)		1/115 (0.9%)
Acute tonsillitis	1/115 (0.9%)		0/115 (0%)
Adenoiditis	1/115 (0.9%)		0/115 (0%)
Gastrointestinal infection	2/115 (1.7%)		0/115 (0%)
Gingival infection	1/115 (0.9%)		0/115 (0%)
Helminthic infection	1/115 (0.9%)		0/115 (0%)
Infected bites	1/115 (0.9%)		0/115 (0%)
Nasopharyngitis	22/115 (19.1%)		24/115 (20.9%)
Upper respiratory tract infection	6/115 (5.2%)		11/115 (9.6%)
Rhinitis	4/115 (3.5%)		8/115 (7%)
Pharyngitis	4/115 (3.5%)		4/115 (3.5%)
Tonsillitis	2/115 (1.7%)		3/115 (2.6%)
Sinusitis	2/115 (1.7%)		5/115 (4.3%)
Viral infection	3/115 (2.6%)		3/115 (2.6%)
Nail infection	0/115 (0%)		2/115 (1.7%)
Respiratory tract infection	1/115 (0.9%)		2/115 (1.7%)
Pneumonia	0/115 (0%)		2/115 (1.7%)
Otitis externa	0/115 (0%)		1/115 (0.9%)
Otitis media	2/115 (1.7%)		1/115 (0.9%)
Parasitic gastroenteritis	0/115 (0%)		1/115 (0.9%)
Skin infection	1/115 (0.9%)		1/115 (0.9%)
Mycoplasma infection	1/115 (0.9%)		0/115 (0%)
Oral candidiasis	1/115 (0.9%)		0/115 (0%)
Oral herpes	1/115 (0.9%)		0/115 (0%)
Pharyngitis streptococcal	1/115 (0.9%)		0/115 (0%)
Rubella	1/115 (0.9%)		0/115 (0%)
Tracheitis	1/115 (0.9%)		0/115 (0%)
Urinary tract infection	2/115 (1.7%)		0/115 (0%)
Injury, poisoning and procedural complications
Arthropod bite	0/115 (0%)		2/115 (1.7%)
Arthropod sting	1/115 (0.9%)		1/115 (0.9%)
Concussion	1/115 (0.9%)		0/115 (0%)
Fall	20/115 (17.4%)		21/115 (18.3%)
Contusion	4/115 (3.5%)		3/115 (2.6%)
Ligament sprain	7/115 (6.1%)		3/115 (2.6%)
Laceration	1/115 (0.9%)		2/115 (1.7%)
Post-traumatic pain	4/115 (3.5%)		2/115 (1.7%)
Spinal compression fracture	1/115 (0.9%)		2/115 (1.7%)
Electrical burn	0/115 (0%)		1/115 (0.9%)
Excoriation	1/115 (0.9%)		1/115 (0.9%)
Fibula fracture	0/115 (0%)		1/115 (0.9%)
Foot fracture	1/115 (0.9%)		1/115 (0.9%)
Hand fracture	1/115 (0.9%)		1/115 (0.9%)
Joint injury	1/115 (0.9%)		1/115 (0.9%)
Muscle injury	0/115 (0%)		1/115 (0.9%)
Muscle strain	0/115 (0%)		1/115 (0.9%)
Scratch	0/115 (0%)		1/115 (0.9%)
Tibia fracture	0/115 (0%)		1/115 (0.9%)
Tooth injury	0/115 (0%)		1/115 (0.9%)
Ulna fracture	0/115 (0%)		1/115 (0.9%)
Upper limb fracture	0/115 (0%)		1/115 (0.9%)
Head injury	1/115 (0.9%)		0/115 (0%)
Limb injury	1/115 (0.9%)		0/115 (0%)
Lip injury	1/115 (0.9%)		0/115 (0%)
Thermal burn	2/115 (1.7%)		0/115 (0%)
Investigations
Renin increased	3/115 (2.6%)		1/115 (0.9%)
Metabolism and nutrition disorders
Hypertriglyceridaemia	3/115 (2.6%)		5/115 (4.3%)
Decreased appetite	2/115 (1.7%)		3/115 (2.6%)
Electrolyte imbalance	1/115 (0.9%)		2/115 (1.7%)
Vitamin D deficiency	0/115 (0%)		2/115 (1.7%)
Abnormal weight gain	1/115 (0.9%)		1/115 (0.9%)
Dyslipidaemia	0/115 (0%)		1/115 (0.9%)
Fluid retention	0/115 (0%)		1/115 (0.9%)
Hypercholesterolaemia	2/115 (1.7%)		1/115 (0.9%)
Hyperlipidaemia	1/115 (0.9%)		1/115 (0.9%)
Iron deficiency	0/115 (0%)		1/115 (0.9%)
Hyperglycaemia	1/115 (0.9%)		0/115 (0%)
Hyperkalaemia	1/115 (0.9%)		0/115 (0%)
Hyperuricaemia	2/115 (1.7%)		0/115 (0%)
Hypervitaminosis D	1/115 (0.9%)		0/115 (0%)
Hypoglycaemia	1/115 (0.9%)		0/115 (0%)
Hyponatraemia	1/115 (0.9%)		0/115 (0%)
Increased appetite	1/115 (0.9%)		0/115 (0%)
Metabolic acidosis	1/115 (0.9%)		0/115 (0%)
Musculoskeletal and connective tissue disorders
Back pain	8/115 (7%)		11/115 (9.6%)
Arthralgia	5/115 (4.3%)		6/115 (5.2%)
Foot deformity	2/115 (1.7%)		3/115 (2.6%)
Growing pains	0/115 (0%)		1/115 (0.9%)
Bone pain	2/115 (1.7%)		0/115 (0%)
Pain in extremity	14/115 (12.2%)		10/115 (8.7%)
Myalgia	0/115 (0%)		3/115 (2.6%)
Musculoskeletal chest pain	2/115 (1.7%)		2/115 (1.7%)
Musculoskeletal pain	2/115 (1.7%)		2/115 (1.7%)
Joint contracture	0/115 (0%)		1/115 (0.9%)
Muscle atrophy	0/115 (0%)		1/115 (0.9%)
Muscle tightness	0/115 (0%)		1/115 (0.9%)
Muscular weakness	1/115 (0.9%)		1/115 (0.9%)
Osteoporosis	0/115 (0%)		1/115 (0.9%)
Scoliosis	2/115 (1.7%)		1/115 (0.9%)
Tendinous contracture	0/115 (0%)		1/115 (0.9%)
Joint crepitation	1/115 (0.9%)		0/115 (0%)
Lordosis	1/115 (0.9%)		0/115 (0%)
Muscle spasms	1/115 (0.9%)		0/115 (0%)
Osteopenia	2/115 (1.7%)		0/115 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	2/115 (1.7%)		1/115 (0.9%)
Nervous system disorders
Headache	21/115 (18.3%)		21/115 (18.3%)
Autism	0/115 (0%)		1/115 (0.9%)
Coordination abnormal	0/115 (0%)		1/115 (0.9%)
Epilepsy	0/115 (0%)		1/115 (0.9%)
Migraine	1/115 (0.9%)		1/115 (0.9%)
Dizziness	1/115 (0.9%)		0/115 (0%)
Hypotonia	1/115 (0.9%)		0/115 (0%)
Sinus headache	0/115 (0%)		2/115 (1.7%)
Petit mal epilepsy	0/115 (0%)		1/115 (0.9%)
Psychomotor hyperactivity	1/115 (0.9%)		1/115 (0.9%)
Restless legs syndrome	0/115 (0%)		1/115 (0.9%)
Tremor	0/115 (0%)		1/115 (0.9%)
Psychiatric disorders
Attention deficit/hyperactivity disorder	1/115 (0.9%)		3/115 (2.6%)
Aggression	0/115 (0%)		2/115 (1.7%)
Sleep disorder	0/115 (0%)		2/115 (1.7%)
Abnormal behaviour	0/115 (0%)		1/115 (0.9%)
Negativism	0/115 (0%)		1/115 (0.9%)
Obsessive-compulsive disorder	1/115 (0.9%)		1/115 (0.9%)
Anxiety	2/115 (1.7%)		0/115 (0%)
Dysphemia	1/115 (0.9%)		0/115 (0%)
Middle insomnia	1/115 (0.9%)		0/115 (0%)
Mood swings	2/115 (1.7%)		0/115 (0%)
Renal and urinary disorders
Haematuria	1/115 (0.9%)		7/115 (6.1%)
Dysuria	3/115 (2.6%)		2/115 (1.7%)
Enuresis	1/115 (0.9%)		2/115 (1.7%)
Bladder trabeculation	0/115 (0%)		1/115 (0.9%)
Flank pain	0/115 (0%)		1/115 (0.9%)
Hypercalciuria	1/115 (0.9%)		0/115 (0%)
Myoglobinuria	1/115 (0.9%)		0/115 (0%)
Nephrolithiasis	2/115 (1.7%)		0/115 (0%)
Urinary incontinence	1/115 (0.9%)		2/115 (1.7%)
Polyuria	0/115 (0%)		1/115 (0.9%)
Renal cyst	0/115 (0%)		1/115 (0.9%)
Urine abnormality	2/115 (1.7%)		1/115 (0.9%)
Pollakiuria	1/115 (0.9%)		0/115 (0%)
Reproductive system and breast disorders
Genital discomfort	0/115 (0%)		1/115 (0.9%)
Respiratory, thoracic and mediastinal disorders
Cough	13/115 (11.3%)		19/115 (16.5%)
Epistaxis	4/115 (3.5%)		7/115 (6.1%)
Oropharyngeal pain	6/115 (5.2%)		7/115 (6.1%)
Nasal congestion	2/115 (1.7%)		3/115 (2.6%)
Rhinorrhoea	3/115 (2.6%)		3/115 (2.6%)
Wheezing	0/115 (0%)		3/115 (2.6%)
Asthmatic crisis	0/115 (0%)		1/115 (0.9%)
Productive cough	0/115 (0%)		1/115 (0.9%)
Sneezing	0/115 (0%)		1/115 (0.9%)
Dyspnoea	1/115 (0.9%)		0/115 (0%)
Sinus congestion	2/115 (1.7%)		0/115 (0%)
Sleep apnoea syndrome	2/115 (1.7%)		0/115 (0%)
Throat irritation	1/115 (0.9%)		0/115 (0%)
Skin and subcutaneous tissue disorders
Blister	0/115 (0%)		1/115 (0.9%)
Acne	1/115 (0.9%)		0/115 (0%)
Dermatitis allergic	1/115 (0.9%)		0/115 (0%)
Rash	4/115 (3.5%)		4/115 (3.5%)
Ingrowing nail	0/115 (0%)		2/115 (1.7%)
Pruritus	2/115 (1.7%)		2/115 (1.7%)
Rash erythematous	1/115 (0.9%)		2/115 (1.7%)
Dry skin	0/115 (0%)		1/115 (0.9%)
Ecchymosis	0/115 (0%)		1/115 (0.9%)
Hair texture abnormal	0/115 (0%)		1/115 (0.9%)
Hirsutism	0/115 (0%)		1/115 (0.9%)
Seborrhoeic dermatitis	0/115 (0%)		1/115 (0.9%)
Skin burning sensation	0/115 (0%)		1/115 (0.9%)
Skin lesion	0/115 (0%)		1/115 (0.9%)
Skin mass	0/115 (0%)		1/115 (0.9%)
Erythema	1/115 (0.9%)		0/115 (0%)
Skin exfoliation	1/115 (0.9%)		0/115 (0%)
Skin hyperpigmentation	1/115 (0.9%)		0/115 (0%)
Vascular disorders
Hypertension	2/115 (1.7%)		1/115 (0.9%)
Hypotension	0/115 (0%)		1/115 (0.9%)
Aortic dilatation	1/115 (0.9%)		0/115 (0%)
Flushing	3/115 (2.6%)		0/115 (0%)
Haematoma	1/115 (0.9%)		0/115 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor can review results and/or communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the sponsor for review. The sponsor may consult with the PI to require changes to the communication or extend the embargo.