Genetic Diseases, Inborn, Genetic Diseases, X-Linked, Muscular Diseases, Muscular Disorders, Atrophic, Muscular Dystrophies, Muscular Dystrophy, Duchenne, Musculoskeletal Diseases, Nervous System Diseases, Neuromuscular Diseases
Conditions
Keywords
Duchenne muscular dystrophy, Dystrophinopathy, Nonsense mutation, Premature stop codon, Becker muscular dystrophy, DMD/BMD, PTC124, Ataluren
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.
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.
Interventions
DRUGAtaluren
Ataluren will be administered as per the dose and schedule specified in the arm.
DRUGPlacebo
Placebo will be administered as per the schedule specified in the arm.
Sponsors
PTC Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
7 Years to 16 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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). |
| 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. |
| 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. |
Countries
Australia, Belgium, Brazil, Canada, Chile, Czechia, France, Germany, Israel, Italy, Poland, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
A total of 291 participants were screened for eligibility, of which 61 participants did not meet entry criteria.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. | 115 |
| Ataluren 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. | 115 |
| Total | 230 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Placebo | Total | Ataluren |
|---|---|---|---|
| 6 Minute Walk Distance (6MWD) | 362.69 meters STANDARD_DEVIATION 81.424 | 363.36 meters STANDARD_DEVIATION 77.322 | 364.04 meters STANDARD_DEVIATION 73.342 |
| Age, Continuous | 9.0 years STANDARD_DEVIATION 1.65 | 8.9 years STANDARD_DEVIATION 1.72 | 8.9 years STANDARD_DEVIATION 1.79 |
| Baseline 6MWT <300 meters | 22 Participants | 47 Participants | 25 Participants |
| Baseline 6MWT >=300 to <400 meters | 52 Participants | 99 Participants | 47 Participants |
| Baseline 6MWT >=400 meters | 41 Participants | 84 Participants | 43 Participants |
| Pediatric Outcomes Data Collection Instrument (PODCI) Scores Sports/Physical Functioning Score | 56.0 units on a scale STANDARD_DEVIATION 20.94 | 56.1 units on a scale STANDARD_DEVIATION 19.92 | 56.2 units on a scale STANDARD_DEVIATION 18.94 |
| Pediatric Outcomes Data Collection Instrument (PODCI) Scores Transfers/Basic Mobility Score | 81.4 units on a scale STANDARD_DEVIATION 15.79 | 82.7 units on a scale STANDARD_DEVIATION 14.53 | 83.9 units on a scale STANDARD_DEVIATION 13.1 |
| Physical Function Total Score as Measured by North Star Ambulatory Assessment (NSAA) | 60.2 units on a scale STANDARD_DEVIATION 18.37 | 60.6 units on a scale STANDARD_DEVIATION 18.14 | 60.9 units on a scale STANDARD_DEVIATION 17.97 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 115 Participants | 230 Participants | 115 Participants |
| Time to Climb 4 Stairs | 6.76 seconds STANDARD_DEVIATION 7.287 | 6.38 seconds STANDARD_DEVIATION 6.389 | 5.99 seconds STANDARD_DEVIATION 5.347 |
| Time to Descend 4 Stairs | 5.05 seconds STANDARD_DEVIATION 5.362 | 5.06 seconds STANDARD_DEVIATION 5.247 | 5.07 seconds STANDARD_DEVIATION 5.157 |
| Time to Walk/Run 10 Meters | 6.83 seconds STANDARD_DEVIATION 2.924 | 6.75 seconds STANDARD_DEVIATION 2.996 | 6.66 seconds STANDARD_DEVIATION 3.078 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 99 / 115 | 103 / 115 |
| serious Total, serious adverse events | 4 / 115 | 4 / 115 |
Outcome results
Primary
Change From Baseline in 6MWD at 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.
Time frame: Baseline, Week 48
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in 6MWD at Week 48 | -60.67 meters | Standard Error 9.323 |
| Ataluren | Change From Baseline in 6MWD at Week 48 | -47.69 meters | Standard Error 9.247 |
Comparison: 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.p-value: 0.21395% CI: [-7.44, 33.39]Mixed Models Analysis
Secondary
Change From Baseline in Time to Climb 4 Stairs at 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.
Time frame: Baseline, Week 48
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Time to Climb 4 Stairs at Week 48 | 4.46 seconds | Standard Deviation 7.31 |
| Ataluren | Change From Baseline in Time to Climb 4 Stairs at Week 48 | 2.65 seconds | Standard Deviation 5.297 |
Secondary
Change From Baseline in Time to Descend 4 Stairs at 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.
Time frame: Baseline, Week 48
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Time to Descend 4 Stairs at Week 48 | 3.97 seconds | Standard Deviation 7.854 |
| Ataluren | Change From Baseline in Time to Descend 4 Stairs at Week 48 | 2.15 seconds | Standard Deviation 5.306 |
Secondary
Change From Baseline in Time to Walk/Run 10 Meters at 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.
Time frame: Baseline, Week 48
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Time to Walk/Run 10 Meters at Week 48 | 3.47 seconds | Standard Deviation 6.393 |
| Ataluren | Change From Baseline in Time to Walk/Run 10 Meters at Week 48 | 2.27 seconds | Standard Deviation 5.216 |
Secondary
Percentage of Participants With Treatment-Emergent Adverse Events (AEs)
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
Population: As-treated population included all randomized participants who actually received any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Treatment-Emergent Adverse Events (AEs) | 87.8 percentage of participants |
| Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (AEs) | 89.6 percentage of participants |
Secondary
Time to 10 Percent (%) Persistent Worsening in 6MWD
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to 10 Percent (%) Persistent Worsening in 6MWD | <300 meters | 56 days |
| Placebo | Time to 10 Percent (%) Persistent Worsening in 6MWD | >=300 to <400 meters | 280 days |
| Placebo | Time to 10 Percent (%) Persistent Worsening in 6MWD | >=400 meters | NA days |
| Ataluren | Time to 10 Percent (%) Persistent Worsening in 6MWD | <300 meters | 164 days |
| Ataluren | Time to 10 Percent (%) Persistent Worsening in 6MWD | >=300 to <400 meters | NA days |
| Ataluren | Time to 10 Percent (%) Persistent Worsening in 6MWD | >=400 meters | NA days |
Other Pre-specified
Ataluren Plasma Concentration
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
Population: As-treated population included all randomized participants who actually received any study treatment. Here, 'Number analyzed 'signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Ataluren Plasma Concentration | Week 16 | 3.429 mcg/mL | Standard Deviation 3.9275 |
| Placebo | Ataluren Plasma Concentration | Week 24 | 3.323 mcg/mL | Standard Deviation 3.6135 |
| Placebo | Ataluren Plasma Concentration | Week 08 | 4.230 mcg/mL | Standard Deviation 5.3913 |
| Placebo | Ataluren Plasma Concentration | Week 32 | 3.480 mcg/mL | Standard Deviation 3.1053 |
| Placebo | Ataluren Plasma Concentration | Week 40 | 3.997 mcg/mL | Standard Deviation 4.7615 |
| Placebo | Ataluren Plasma Concentration | Week 48 | 3.544 mcg/mL | Standard Deviation 3.8082 |
Other Pre-specified
Change From Baseline in Physical Function Total Score as Measured by NSAA at 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.
Time frame: Baseline, Week 48
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Physical Function Total Score as Measured by NSAA at Week 48 | -8.4 units on a scale | Standard Deviation 10.65 |
| Ataluren | Change From Baseline in Physical Function Total Score as Measured by NSAA at Week 48 | -6.3 units on a scale | Standard Deviation 10.64 |
Other Pre-specified
Change From Baseline in PODCI Transfers/Basic Mobility and Sports/Physical Functioning Scores at 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.
Time frame: Baseline, Week 48
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in PODCI Transfers/Basic Mobility and Sports/Physical Functioning Scores at Week 48 | Transfers/Basic Mobility Score | -8.8 units on a scale | Standard Deviation 15.8 |
| Placebo | Change From Baseline in PODCI Transfers/Basic Mobility and Sports/Physical Functioning Scores at Week 48 | Sports/Physical Functioning Score | -7.3 units on a scale | Standard Deviation 15.87 |
| Ataluren | Change From Baseline in PODCI Transfers/Basic Mobility and Sports/Physical Functioning Scores at Week 48 | Transfers/Basic Mobility Score | -6.6 units on a scale | Standard Deviation 14.76 |
| Ataluren | Change From Baseline in PODCI Transfers/Basic Mobility and Sports/Physical Functioning Scores at Week 48 | Sports/Physical Functioning Score | -5.6 units on a scale | Standard Deviation 15.91 |
Other Pre-specified
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
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
Population: 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 | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | 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 | Sleep | Slightly better | 4 Participants |
| Placebo | 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 | Cognition/Social Functioning | Unchanged | 71 Participants |
| Placebo | 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 | Cognition/Social Functioning | Slightly worse | 3 Participants |
| Placebo | 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 | Emotional/Social Functioning | Much better | 3 Participants |
| Placebo | 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 | General Energy Level | Slightly better | 12 Participants |
| Placebo | 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 | Physical Functioning: Other | Much better | 4 Participants |
| Placebo | 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 | Physical Functioning: Other | Slightly worse | 7 Participants |
| Placebo | 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 | Physical Functioning: Other | Much worse | 7 Participants |
| Placebo | 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 | Cognition/Social Functioning | Much better | 6 Participants |
| Placebo | 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 | Cognition/Social Functioning | Slightly better | 12 Participants |
| Placebo | 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 | Physical Functioning: Upper Extremity Activity | Much better | 1 Participants |
| Placebo | 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 | Physical Functioning: Upper Extremity Activity | Slightly better | 7 Participants |
| Placebo | 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 | Physical Functioning: Upper Extremity Activity | Unchanged | 67 Participants |
| Placebo | 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 | Physical Functioning: Upper Extremity Activity | Slightly worse | 6 Participants |
| Placebo | 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 | Physical Functioning: Upper Extremity Activity | Much worse | 1 Participants |
| Placebo | 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 | Physical Functioning: Walking | Much better | 5 Participants |
| Placebo | 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 | Physical Functioning: Walking | Slightly better | 13 Participants |
| Placebo | 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 | Physical Functioning: Walking | Unchanged | 57 Participants |
| Placebo | 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 | Physical Functioning: Walking | Slightly worse | 19 Participants |
| Placebo | 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 | Physical Functioning: Walking | Much worse | 18 Participants |
| Placebo | 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 | Physical Functioning: Climbing Stairs | Much better | 4 Participants |
| Placebo | 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 | Physical Functioning: Climbing Stairs | Slightly better | 8 Participants |
| Placebo | 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 | Physical Functioning: Climbing Stairs | Unchanged | 61 Participants |
| Placebo | 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 | Physical Functioning: Climbing Stairs | Slightly worse | 17 Participants |
| Placebo | 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 | Physical Functioning: Other | Slightly better | 9 Participants |
| Placebo | 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 | Physical Functioning: Other | Unchanged | 38 Participants |
| Placebo | 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 | Physical Functioning: Climbing Stairs | Much worse | 15 Participants |
| Placebo | 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 | General Energy Level | Unchanged | 54 Participants |
| Placebo | 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 | General Energy Level | Slightly worse | 11 Participants |
| Placebo | 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 | General Energy Level | Much worse | 3 Participants |
| Placebo | 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 | Cognition/Social Functioning | Much worse | 0 Participants |
| Placebo | 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 | Emotional/Social Functioning | Slightly better | 9 Participants |
| Placebo | 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 | Emotional/Social Functioning | Unchanged | 75 Participants |
| Placebo | 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 | Sleep | Much better | 3 Participants |
| Placebo | 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 | Sleep | Unchanged | 73 Participants |
| Placebo | 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 | Emotional/Social Functioning | Slightly worse | 5 Participants |
| Placebo | 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 | Emotional/Social Functioning | Much worse | 2 Participants |
| Placebo | 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 | General Energy Level | Much better | 3 Participants |
| Placebo | 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 | Sleep | Slightly worse | 5 Participants |
| Placebo | 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 | Sleep | Much worse | 0 Participants |
| Placebo | 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 | Other | Much better | 0 Participants |
| Placebo | 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 | Other | Slightly better | 5 Participants |
| Placebo | 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 | Other | Unchanged | 15 Participants |
| Placebo | 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 | Other | Slightly worse | 2 Participants |
| Placebo | 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 | Other | Much worse | 1 Participants |
| Ataluren | 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 | Physical Functioning: Other | Much better | 5 Participants |
| Ataluren | 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 | Cognition/Social Functioning | Slightly better | 20 Participants |
| Ataluren | 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 | Sleep | Much worse | 2 Participants |
| Ataluren | 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 | Cognition/Social Functioning | Unchanged | 74 Participants |
| Ataluren | 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 | Physical Functioning: Other | Slightly better | 10 Participants |
| Ataluren | 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 | Cognition/Social Functioning | Slightly worse | 3 Participants |
| Ataluren | 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 | Cognition/Social Functioning | Much worse | 2 Participants |
| Ataluren | 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 | Other | Unchanged | 13 Participants |
| Ataluren | 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 | Emotional/Social Functioning | Slightly better | 21 Participants |
| Ataluren | 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 | Emotional/Social Functioning | Unchanged | 68 Participants |
| Ataluren | 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 | Physical Functioning: Climbing Stairs | Slightly worse | 15 Participants |
| Ataluren | 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 | Emotional/Social Functioning | Slightly worse | 6 Participants |
| Ataluren | 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 | Physical Functioning: Climbing Stairs | Much worse | 13 Participants |
| Ataluren | 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 | Physical Functioning: Other | Slightly worse | 8 Participants |
| Ataluren | 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 | General Energy Level | Much better | 8 Participants |
| Ataluren | 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 | General Energy Level | Slightly better | 12 Participants |
| Ataluren | 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 | Cognition/Social Functioning | Much better | 5 Participants |
| Ataluren | 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 | Other | Much better | 1 Participants |
| Ataluren | 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 | General Energy Level | Unchanged | 63 Participants |
| Ataluren | 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 | Physical Functioning: Upper Extremity Activity | Much better | 4 Participants |
| Ataluren | 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 | Emotional/Social Functioning | Much worse | 2 Participants |
| Ataluren | 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 | Physical Functioning: Upper Extremity Activity | Slightly better | 7 Participants |
| Ataluren | 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 | General Energy Level | Slightly worse | 5 Participants |
| Ataluren | 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 | Physical Functioning: Upper Extremity Activity | Unchanged | 73 Participants |
| Ataluren | 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 | Other | Much worse | 0 Participants |
| Ataluren | 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 | Physical Functioning: Upper Extremity Activity | Slightly worse | 2 Participants |
| Ataluren | 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 | Sleep | Unchanged | 76 Participants |
| Ataluren | 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 | Physical Functioning: Upper Extremity Activity | Much worse | 2 Participants |
| Ataluren | 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 | Emotional/Social Functioning | Much better | 8 Participants |
| Ataluren | 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 | Physical Functioning: Walking | Much better | 8 Participants |
| Ataluren | 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 | Other | Slightly better | 6 Participants |
| Ataluren | 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 | Physical Functioning: Walking | Slightly better | 16 Participants |
| Ataluren | 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 | Sleep | Slightly worse | 2 Participants |
| Ataluren | 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 | Physical Functioning: Walking | Unchanged | 60 Participants |
| Ataluren | 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 | Physical Functioning: Other | Unchanged | 44 Participants |
| Ataluren | 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 | Physical Functioning: Walking | Slightly worse | 21 Participants |
| Ataluren | 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 | Sleep | Much better | 3 Participants |
| Ataluren | 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 | Physical Functioning: Walking | Much worse | 3 Participants |
| Ataluren | 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 | General Energy Level | Much worse | 1 Participants |
| Ataluren | 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 | Physical Functioning: Climbing Stairs | Much better | 4 Participants |
| Ataluren | 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 | Other | Slightly worse | 3 Participants |
| Ataluren | 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 | Physical Functioning: Climbing Stairs | Slightly better | 13 Participants |
| Ataluren | 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 | Physical Functioning: Other | Much worse | 1 Participants |
| Ataluren | 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 | Physical Functioning: Climbing Stairs | Unchanged | 65 Participants |
| Ataluren | 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 | Sleep | Slightly better | 8 Participants |
Other Pre-specified
Study Drug Compliance
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
Population: As-treated population included all randomized participants who actually received any study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Study Drug Compliance | 95.1 percentage of drug | Standard Deviation 9.43 |
| Ataluren | Study Drug Compliance | 95.7 percentage of drug | Standard Deviation 7.57 |