Becker Muscular Dystrophy, Duchenne Muscular Dystrophy
Conditions
Keywords
Duchenne muscular dystrophy, Becker muscular dystrophy, Nonsense mutation, Premature stop codon, DMD/BMD, PTC124
Brief summary
DMD/BMD is a genetic disorder that 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 during childhood and teenage years. A specific type of mutation, called a nonsense (premature stop codon) mutation is the cause of DMD/BMD in approximately 13 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. This study is a Phase 2b trial that will evaluate the clinical benefit of ataluren in boys with DMD/BMD due to a nonsense mutation. The main goals of the study are to understand whether ataluren can improve walking, activity, muscle function, and strength and whether the drug can safely be given for a long period of time.
Detailed description
This study is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, efficacy and safety study, designed to document the clinical benefit of ataluren when administered as therapy of patients with DMD/BMD due to a nonsense mutation (premature stop codon) in the dystrophin gene.
Interventions
DRUGAtaluren
Ataluren will be administered as per the dose and schedule specified in the respective arms.
DRUGPlacebo
Placebo matching to ataluren will be administered as the schedule specified in the respective 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
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if \<18 years of age). * Male sex. * Age ≥5 years. * Phenotypic evidence of DMD/BMD based on the onset of characteristic clinical symptoms or signs (that is, proximal muscle weakness, waddling gait, and Gowers' maneuver) by 9 years of age, an elevated serum CK level, and ongoing difficulty with ambulation. * 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. * Ability to walk ≥75 meters unassisted during the screening 6-minute walk test. Note: Other personal assistance or use of assistive devices for ambulation (for example, short leg braces, long leg braces or walkers) were not permitted. * Confirmed screening laboratory values within the central laboratory ranges (hepatic, adrenal, renal, and serum electrolytes parameters). * In participants who were sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 6-week follow-up periods. * Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions. Note: Psychological, social, familial, or geographical factors that might preclude adequate study participation (in particular, the ability to satisfactorily perform the 6MWT) should have been considered.
Exclusion criteria
* Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment. * Initiation of systemic corticosteroid therapy within 6 months prior to start of study treatment or change in systemic corticosteroid therapy (for example, initiation, change in type of drug, dose modification not related to body weight change, schedule modification, interruption, discontinuation, 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 within 3 months prior to start of study treatment. * Treatment with warfarin within 1 month prior to start of study treatment. * Prior therapy with ataluren. * Known hypersensitivity to any of the ingredients or excipients of the study drug (Litesse® UltraTM \[refined polydextrose\], polyethylene glycol 3350, Lutrol® micro F127 \[poloxamer 407\], mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, Cab-O-Sil® M5P \[colloidal silica\], magnesium stearate). * Exposure to another investigational drug within 2 months prior to start of study treatment. * History of major surgical procedure within 30 days prior to start of study treatment. * Ongoing immunosuppressive therapy (other than corticosteroids). * Ongoing participation in any other therapeutic clinical trial. * Expectation of major surgical procedure (for example, scoliosis surgery) during the 12-month treatment period of the study. * Requirement for daytime ventilator assistance. * Clinical symptoms and signs of congestive heart failure (American College of Cardiology/American Heart Association Stage C or Stage D) or evidence on echocardiogram of clinically significant myopathy. * Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram 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 was performed in a 30 meters long flat corridor, where the participant was 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Time to Stand From Supine Position at Week 48 | Baseline, Week 48 | If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. Change from baseline data has been reported. |
| Change From Baseline in Time to Walk/Run 10 Meters at Week 48 | Baseline, Week 48 | If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. Change from baseline data has been reported. |
| Change From Baseline in Time to Climb 4 Stairs at Week 48 | Baseline, Week 48 | If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. Change from baseline data has been reported. |
| Change From Baseline in Time to Descend 4 Stairs at Week 48 | Baseline, Week 48 | If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. Change from baseline data has been reported. |
| Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Baseline, Week 48 | Upper and lower extremity myometry was performed using a myometer following standardized procedures. Muscle groups evaluated included knee flexors, knee extensors, elbow flexors, elbow extensors, and shoulder abductors. Bilateral assessments were done and 3 measurements were recorded from each muscle group on each side if possible. Mean values for the left and right sides were calculated. |
| Change From Baseline in Mean Activity Period/Day/Visit at Week 48, as Assessed by Step Activity Monitoring (SAM) | Baseline, Week 48 | The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean activity period/day/visit was computed for each participant. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as the first time after 3:00 AM that greater than (\>) 2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was less than (\<) 50 percent (%) of the mean active period across all days for that participant's visit. |
| Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 48, as Assessed by SAM | Baseline, Week 48 | The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean total step count/day/visit during the active periods was computed for each participant. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as the first time after 3:00 AM that \>2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was \<50% of the mean active period across all days for that participant's visit. |
| Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 48, as Assessed by SAM | Baseline, Week 48 | The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean total step count/hour during the active periods for the days in a visit was computed for each participant. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as the first time after 3:00 AM that \>2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was \<50% of the mean active period across all days for that participant's visit. |
| Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Baseline, Week 48 | SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). The maximum continuous 10-minute, 20-minute, 30-minute, and 60-minute total step counts were computed for each participant. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as the first time after 3:00 AM that \>2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was \<50% of the mean active period across all days for that participant's visit. |
| Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Baseline, Week 48 | SAM is a pedometer(worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again. Proportion of time during active periods spent at low activity(≤15 steps/minute), medium activity(16-30 steps/minute), and high activity(\>30 steps/minute) were computed for each participant. Mean obtained during Screening and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as first time after 3:00 AM that \>2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was \<50% of the mean active period across all days for that participant's visit. |
| Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 48 | Baseline, Week 48 | Blood samples collected for chemistry assays were used to quantify serum CK concentrations. Serum CK was assessed as a potential biomarker for muscle fragility, with a reduction in serum CK considered to be a positive outcome. |
| Percent Change From Pre-Treatment Visit (1 Week Prior to Baseline Visit) in Biceps Muscle Dystrophin Expression at Post-Treatment Visit (Week 36), as Determined by Immunofluorescence | Pre-Treatment (1 week prior to baseline), post-treatment (Week 36) | Immunofluorescence evidence of a change in dystrophin expression on biceps muscle biopsy was defined as an increase in the staining of the sarcolemmal membrane with an antibody to the C-terminal portion of the dystrophin protein (excluding revertant fibers) between the pre-treatment (1 week prior to Baseline visit) and post-treatment (Week 36) biopsies. The biceps muscle was biopsied from one arm for confirmation of the absence or reduced levels of dystrophin prior to treatment initiation and from the other arm to assess for production of dystrophin post-treatment. |
| Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline, Week 48 | HRQL was measured via the PedsQL. The generic core module (including physical, emotional, social and school functioning scales) comprises 23 questions and the fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. The PedsQL was completed by both the participant and/or a parent/caregiver. Examples of items in each of the generic core module scales include: It is hard for me to run; I feel sad or blue; I cannot do things that other kids my age can do; and It is hard to pay attention in class. Each of the generic core module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating better health-related quality of life. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48. |
| Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline, Week 48 | HRQL was measured via the PedsQL. The generic core module (including physical, emotional, social and school functioning scales) comprises 23 questions and the fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. The PedsQL was completed by both the participant and/or a parent/caregiver. Examples of items in each of the generic core module scales include: It is hard for me to run; I feel sad or blue; I cannot do things that other kids my age can do; and It is hard to pay attention in class. Each of the generic core module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating better health-related quality of life. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48. |
| Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 | Baseline, Week 48 | HRQL was measured via the PedsQL. The fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. PedsQL was completed by both the participant and/or a parent/caregiver. Fatigue-specific module obtains information relating to items such as: I feel too tired to do things that I like to do; I spend a lot of time in bed; and I have trouble remembering more than one thing at a time; Each of the fatigue-specific module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating less fatigue. Total score was the sum of all items over the number of items answered on all scales. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48. |
| Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 | Baseline, Week 48 | HRQL was measured via the PedsQL. The fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. The PedsQL was completed by both the participant and/or a parent/caregiver. Fatigue-specific module obtains information relating to items such as: I feel too tired to do things that I like to do; I spend a lot of time in bed; and I have trouble remembering more than one thing at a time; Each of the fatigue-specific module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating less fatigue. Total score was the sum of all items over the number of items answered on all scales. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48. |
| Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score | Week 48 | TSQM consisted of 14 questions about treatment satisfaction with drug in 4 domains: Effectiveness (Questions 1-3 scored as 1 \[extremely dissatisfied\] to 7 \[extremely satisfied\]), Side Effects (question 4 scored as 0 \[no\] or 1 \[yes\]; question 5 scored as 1 \[extremely bothersome\] to 5 \[not at all bothersome\]; questions 6 - 8 scored as 1 \[a great deal\] to 5 \[not at all\]), Convenience (questions 9 and 10 scored as 1 \[extremely difficult\] to 7 \[extremely easy\]; question 11 scored as 1 \[extremely inconvenient\] to 5 \[extremely convenient\]) and Global Satisfaction (question 12 scored as 1 \[not at all confident\] to 7 \[extremely confident\]; question 13 scored as 1 \[not at all certain\] to 5 \[extremely certain\]; question 14 scored as 1 \[extremely dissatisfied\] to 5 \[extremely satisfied\]). The scores of each of the domains were added together and an algorithm was used to create a score of 0 to 100, with higher scores indicating better treatment satisfaction. |
| Change From Baseline in Participant/Caregiver-Reported Number of Daily Accidental Falls at Week 48 | Baseline, Week 48 | Number of falls was determined by daily diary records maintained by participants and/or parent/caregivers. |
| Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 | Baseline, Week 48 | Basic attention and working memory was measured using the digit span task. A series of digits (0-9) were presented to the child in an auditory format only. The task had 2 parts; in the forward condition, the child was requested to repeat back the digits in the order they were presented and in the backward condition, he was requested to reverse the order of presentation. A raw score of the total number of correct responses was converted to an age-scaled-score (z-score) by subtracting the corresponding mean and dividing by the corresponding standard deviation of a reference population for that age. |
| Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline, Week 48 | The heart rate was measured with a Polar RS400 heart rate monitor, which consists of a transmitter strap worn around the chest and a wristwatch receiver. The monitor produces a digital text file with 1 value per minute that represents the mean heart rate for that minute. Mean heart rates values were collected prior to, during, and after the 6MWT. The participant rested for 5 minutes in a sitting position prior to the 6MWT, and the mean heart rate for the last minute of this rest period was collected and documented as the resting heart rate. During the 6MWT, the mean heart rate was collected and documented as the active heart rate. After completing the 6MWT and resting for 3 minutes, the mean heart rate for 1 minute was collected and documented as the recovery heart rate. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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'. |
| Study Drug Compliance | Baseline to Week 48 | Study drug compliance was assessed by participant daily diary and 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. |
Countries
Australia, Belgium, Canada, France, Germany, Israel, Italy, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
A total of 185 participants were screened for eligibility, of which 11 participants did not meet entry criteria.
Pre-assignment details
A total of 174 eligible participants were randomized in 1:1:1 ratio to receive either placebo, low-dose ataluren, or high-dose ataluren.
Participants by arm
| Arm | Count |
|---|---|
| High-Dose Ataluren Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks. | 60 |
| Low-Dose 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. | 57 |
| Placebo Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. | 57 |
| Total | 174 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Protocol Noncompliance | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo | Low-Dose Ataluren | High-Dose Ataluren |
|---|---|---|---|---|
| 6-Minute Walk Distance (6MWD) | 356.0 meters STANDARD_DEVIATION 96.3 | 359.6 meters STANDARD_DEVIATION 87.67 | 350.0 meters STANDARD_DEVIATION 97.55 | 358.2 meters STANDARD_DEVIATION 103.97 |
| Age, Continuous | 8.5 years STANDARD_DEVIATION 2.59 | 8.3 years STANDARD_DEVIATION 2.33 | 8.8 years STANDARD_DEVIATION 2.91 | 8.4 years STANDARD_DEVIATION 2.53 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 174 Participants | 57 Participants | 57 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 58 / 60 | 56 / 57 | 57 / 57 |
| serious Total, serious adverse events | 2 / 60 | 2 / 57 | 3 / 57 |
Outcome results
Primary
Change From Baseline in 6MWD at Week 48
The 6MWD test was performed in a 30 meters long flat corridor, where the participant was 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 frame: Baseline, Week 48
Population: Intent-to-treat (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 |
|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in 6MWD at Week 48 | -41.81 meters | Standard Deviation 89.234 |
| Low-Dose Ataluren | Change From Baseline in 6MWD at Week 48 | -12.86 meters | Standard Deviation 72.007 |
| Placebo | Change From Baseline in 6MWD at Week 48 | -42.56 meters | Standard Deviation 90.046 |
Comparison: Analysis was performed using mixed model for repeated measures (MMRM) method including rank transformed 6MWD as the dependent variable; and rank transformed baseline 6MWD, treatment, visit, age (less than \[\<\] 9 years versus \[vs.\] greater than or equal to \[\>=\] 9 years) and corticosteroid use (yes vs. no) stratification factors, and interaction between treatment and visit as independent variables.p-value: 0.475695% CI: [-114.8, 53.75]Mixed Models Analysis
Comparison: Analysis was performed using MMRM method including rank transformed 6MWD as the dependent variable; and rank transformed baseline 6MWD, treatment, visit, age (\< 9 years vs. \>= 9 years) and corticosteroid use (yes vs. no) stratification factors, and interaction between treatment and visit as independent variables.p-value: 0.14995% CI: [-22.66, 147.96]Mixed Models Analysis
Secondary
Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry
Upper and lower extremity myometry was performed using a myometer following standardized procedures. Muscle groups evaluated included knee flexors, knee extensors, elbow flexors, elbow extensors, and shoulder abductors. Bilateral assessments were done and 3 measurements were recorded from each muscle group on each side if possible. Mean values for the left and right sides were calculated.
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 | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Baseline: Force during elbow extension | 6.81 pounds | Standard Deviation 3.815 |
| High-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Change at Week 48: Force during knee extension | -0.59 pounds | Standard Deviation 3.511 |
| High-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Baseline: Force during knee flexion | 12.45 pounds | Standard Deviation 4.684 |
| High-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Baseline: Force exerted during elbow flexion | 8.72 pounds | Standard Deviation 4.709 |
| High-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Change at Week 48: Force during elbow extension | -0.28 pounds | Standard Deviation 1.473 |
| High-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Change at Week 48: Force during elbow flexion | -0.50 pounds | Standard Deviation 1.832 |
| High-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Baseline: Force during knee extension | 12.71 pounds | Standard Deviation 7.91 |
| High-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Change at Week 48: Force during knee flexion | 0.39 pounds | Standard Deviation 3.148 |
| Low-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Change at Week 48: Force during elbow extension | 0.10 pounds | Standard Deviation 1.493 |
| Low-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Baseline: Force during knee flexion | 12.08 pounds | Standard Deviation 4.217 |
| Low-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Change at Week 48: Force during knee flexion | -0.07 pounds | Standard Deviation 3.511 |
| Low-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Baseline: Force during knee extension | 12.81 pounds | Standard Deviation 5.753 |
| Low-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Change at Week 48: Force during knee extension | -0.63 pounds | Standard Deviation 3.616 |
| Low-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Baseline: Force exerted during elbow flexion | 7.66 pounds | Standard Deviation 3.154 |
| Low-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Change at Week 48: Force during elbow flexion | -0.10 pounds | Standard Deviation 1.68 |
| Low-Dose Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Baseline: Force during elbow extension | 6.19 pounds | Standard Deviation 3.083 |
| Placebo | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Change at Week 48: Force during elbow extension | -0.51 pounds | Standard Deviation 2.333 |
| Placebo | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Change at Week 48: Force during knee flexion | 0.38 pounds | Standard Deviation 2.991 |
| Placebo | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Change at Week 48: Force during elbow flexion | -0.35 pounds | Standard Deviation 1.807 |
| Placebo | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Baseline: Force during knee extension | 12.96 pounds | Standard Deviation 6.162 |
| Placebo | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Baseline: Force during knee flexion | 11.06 pounds | Standard Deviation 3.494 |
| Placebo | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Baseline: Force during elbow extension | 6.77 pounds | Standard Deviation 2.785 |
| Placebo | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Change at Week 48: Force during knee extension | -1.85 pounds | Standard Deviation 3.899 |
| Placebo | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry | Baseline: Force exerted during elbow flexion | 8.14 pounds | Standard Deviation 2.972 |
Secondary
Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400
The heart rate was measured with a Polar RS400 heart rate monitor, which consists of a transmitter strap worn around the chest and a wristwatch receiver. The monitor produces a digital text file with 1 value per minute that represents the mean heart rate for that minute. Mean heart rates values were collected prior to, during, and after the 6MWT. The participant rested for 5 minutes in a sitting position prior to the 6MWT, and the mean heart rate for the last minute of this rest period was collected and documented as the resting heart rate. During the 6MWT, the mean heart rate was collected and documented as the active heart rate. After completing the 6MWT and resting for 3 minutes, the mean heart rate for 1 minute was collected and documented as the recovery heart rate.
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 this outcome measure for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Resting heart rate | 105.47 beats/minute | Standard Deviation 12.908 |
| High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 48: Resting heart rate | -0.63 beats/minute | Standard Deviation 13.008 |
| High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Active heart rate | 142.67 beats/minute | Standard Deviation 18.07 |
| High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 48: Active heart rate | -5.00 beats/minute | Standard Deviation 21.976 |
| High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Recovery heart rate | 109.90 beats/minute | Standard Deviation 12.633 |
| High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 48: Recovery heart rate | -0.23 beats/minute | Standard Deviation 13.475 |
| Low-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 48: Recovery heart rate | -1.33 beats/minute | Standard Deviation 13.27 |
| Low-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Resting heart rate | 109.70 beats/minute | Standard Deviation 9.908 |
| Low-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 48: Active heart rate | 2.39 beats/minute | Standard Deviation 19.095 |
| Low-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Recovery heart rate | 113.48 beats/minute | Standard Deviation 10.34 |
| Low-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 48: Resting heart rate | -0.36 beats/minute | Standard Deviation 10.223 |
| Low-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Active heart rate | 141.77 beats/minute | Standard Deviation 15.574 |
| Placebo | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 48: Resting heart rate | -0.26 beats/minute | Standard Deviation 15.614 |
| Placebo | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Active heart rate | 136.67 beats/minute | Standard Deviation 20.713 |
| Placebo | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 48: Recovery heart rate | 0.54 beats/minute | Standard Deviation 15.181 |
| Placebo | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 48: Active heart rate | 1.65 beats/minute | Standard Deviation 21.295 |
| Placebo | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Resting heart rate | 104.07 beats/minute | Standard Deviation 11.588 |
| Placebo | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Recovery heart rate | 107.86 beats/minute | Standard Deviation 12.066 |
Secondary
Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM
SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). The maximum continuous 10-minute, 20-minute, 30-minute, and 60-minute total step counts were computed for each participant. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as the first time after 3:00 AM that \>2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was \<50% of the mean active period across all days for that participant's visit.
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 this outcome measure for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Baseline: 60-minute total step count | 18.58 steps | Standard Deviation 6.21 |
| High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Change at Week 48: 10-minute total step count | -2.77 steps | Standard Deviation 8.569 |
| High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Baseline: 20-minute total step count | 29.13 steps | Standard Deviation 9.272 |
| High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Change at Week 48: 20-minute total step count | -2.49 steps | Standard Deviation 7.407 |
| High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Baseline: 30-minute total step count | 25.00 steps | Standard Deviation 8.053 |
| High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Change at Week 48: 30-minute total step count | -2.08 steps | Standard Deviation 6.519 |
| High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Change at Week 48: 60-minute total step count | -1.50 steps | Standard Deviation 5.177 |
| High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Baseline: 10-minute total step count | 35.77 steps | Standard Deviation 10.222 |
| Low-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Baseline: 20-minute total step count | 25.68 steps | Standard Deviation 10.038 |
| Low-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Change at Week 48: 60-minute total step count | -1.85 steps | Standard Deviation 4.616 |
| Low-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Change at Week 48: 20-minute total step count | -2.40 steps | Standard Deviation 5.806 |
| Low-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Baseline: 30-minute total step count | 22.08 steps | Standard Deviation 9.206 |
| Low-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Change at Week 48: 30-minute total step count | -2.31 steps | Standard Deviation 5.505 |
| Low-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Baseline: 60-minute total step count | 16.52 steps | Standard Deviation 7.199 |
| Low-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Baseline: 10-minute total step count | 32.24 steps | Standard Deviation 11.374 |
| Low-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Change at Week 48: 10-minute total step count | -2.79 steps | Standard Deviation 6.355 |
| Placebo | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Change at Week 48: 10-minute total step count | -3.97 steps | Standard Deviation 9.72 |
| Placebo | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Baseline: 30-minute total step count | 25.70 steps | Standard Deviation 7.35 |
| Placebo | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Baseline: 10-minute total step count | 36.76 steps | Standard Deviation 8.935 |
| Placebo | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Change at Week 48: 20-minute total step count | -3.55 steps | Standard Deviation 8.677 |
| Placebo | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Change at Week 48: 60-minute total step count | -2.33 steps | Standard Deviation 6.241 |
| Placebo | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Baseline: 60-minute total step count | 19.50 steps | Standard Deviation 5.887 |
| Placebo | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Baseline: 20-minute total step count | 29.74 steps | Standard Deviation 8.205 |
| Placebo | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM | Change at Week 48: 30-minute total step count | -3.03 steps | Standard Deviation 7.604 |
Secondary
Change From Baseline in Mean Activity Period/Day/Visit at Week 48, as Assessed by Step Activity Monitoring (SAM)
The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean activity period/day/visit was computed for each participant. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as the first time after 3:00 AM that greater than (\>) 2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was less than (\<) 50 percent (%) of the mean active period across all days for that participant's visit.
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 this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Mean Activity Period/Day/Visit at Week 48, as Assessed by Step Activity Monitoring (SAM) | Baseline | 756.84 minutes | Standard Deviation 84.612 |
| High-Dose Ataluren | Change From Baseline in Mean Activity Period/Day/Visit at Week 48, as Assessed by Step Activity Monitoring (SAM) | Change at Week 48 | 0.87 minutes | Standard Deviation 57.833 |
| Low-Dose Ataluren | Change From Baseline in Mean Activity Period/Day/Visit at Week 48, as Assessed by Step Activity Monitoring (SAM) | Baseline | 761.86 minutes | Standard Deviation 76.984 |
| Low-Dose Ataluren | Change From Baseline in Mean Activity Period/Day/Visit at Week 48, as Assessed by Step Activity Monitoring (SAM) | Change at Week 48 | -22.23 minutes | Standard Deviation 84.759 |
| Placebo | Change From Baseline in Mean Activity Period/Day/Visit at Week 48, as Assessed by Step Activity Monitoring (SAM) | Baseline | 751.71 minutes | Standard Deviation 60.513 |
| Placebo | Change From Baseline in Mean Activity Period/Day/Visit at Week 48, as Assessed by Step Activity Monitoring (SAM) | Change at Week 48 | -19.91 minutes | Standard Deviation 91.96 |
Secondary
Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 48, as Assessed by SAM
The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean total step count/day/visit during the active periods was computed for each participant. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as the first time after 3:00 AM that \>2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was \<50% of the mean active period across all days for that participant's visit.
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 this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 48, as Assessed by SAM | Baseline | 5302.31 steps/day | Standard Deviation 1907.058 |
| High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 48, as Assessed by SAM | Change at Week 48 | -615.14 steps/day | Standard Deviation 1468.452 |
| Low-Dose Ataluren | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 48, as Assessed by SAM | Baseline | 4870.13 steps/day | Standard Deviation 2165.522 |
| Low-Dose Ataluren | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 48, as Assessed by SAM | Change at Week 48 | -676.46 steps/day | Standard Deviation 1717.535 |
| Placebo | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 48, as Assessed by SAM | Baseline | 5602.31 steps/day | Standard Deviation 2023.543 |
| Placebo | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 48, as Assessed by SAM | Change at Week 48 | -908.34 steps/day | Standard Deviation 1999.969 |
Secondary
Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 48, as Assessed by SAM
The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean total step count/hour during the active periods for the days in a visit was computed for each participant. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as the first time after 3:00 AM that \>2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was \<50% of the mean active period across all days for that participant's visit.
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 this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 48, as Assessed by SAM | Baseline | 423.67 steps/hour | Standard Deviation 168.754 |
| High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 48, as Assessed by SAM | Change at Week 48 | -44.51 steps/hour | Standard Deviation 125.154 |
| Low-Dose Ataluren | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 48, as Assessed by SAM | Baseline | 383.62 steps/hour | Standard Deviation 161.911 |
| Low-Dose Ataluren | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 48, as Assessed by SAM | Change at Week 48 | -42.23 steps/hour | Standard Deviation 126.429 |
| Placebo | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 48, as Assessed by SAM | Baseline | 446.37 steps/hour | Standard Deviation 160.666 |
| Placebo | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 48, as Assessed by SAM | Change at Week 48 | -59.62 steps/hour | Standard Deviation 153.054 |
Secondary
Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48
Basic attention and working memory was measured using the digit span task. A series of digits (0-9) were presented to the child in an auditory format only. The task had 2 parts; in the forward condition, the child was requested to repeat back the digits in the order they were presented and in the backward condition, he was requested to reverse the order of presentation. A raw score of the total number of correct responses was converted to an age-scaled-score (z-score) by subtracting the corresponding mean and dividing by the corresponding standard deviation of a reference population for that age.
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 this outcome measure for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 | Baseline: Forward condition | 3.59 z-score | Standard Deviation 2.554 |
| High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 | Change at Week 48: Backward condition | 0.56 z-score | Standard Deviation 1.5 |
| High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 | Change at Week 48: Forward condition | 0.39 z-score | Standard Deviation 1.677 |
| High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 | Baseline: Backward condition | 1.73 z-score | Standard Deviation 1.846 |
| Low-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 | Change at Week 48: Backward condition | 0.33 z-score | Standard Deviation 1.441 |
| Low-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 | Baseline: Forward condition | 2.89 z-score | Standard Deviation 2.18 |
| Low-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 | Change at Week 48: Forward condition | 0.50 z-score | Standard Deviation 1.767 |
| Low-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 | Baseline: Backward condition | 1.70 z-score | Standard Deviation 1.868 |
| Placebo | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 | Change at Week 48: Forward condition | 0.40 z-score | Standard Deviation 1.55 |
| Placebo | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 | Change at Week 48: Backward condition | 0.59 z-score | Standard Deviation 1.203 |
| Placebo | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 | Baseline: Backward condition | 1.59 z-score | Standard Deviation 1.46 |
| Placebo | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 | Baseline: Forward condition | 2.84 z-score | Standard Deviation 1.675 |
Secondary
Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48
HRQL was measured via the PedsQL. The generic core module (including physical, emotional, social and school functioning scales) comprises 23 questions and the fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. The PedsQL was completed by both the participant and/or a parent/caregiver. Examples of items in each of the generic core module scales include: It is hard for me to run; I feel sad or blue; I cannot do things that other kids my age can do; and It is hard to pay attention in class. Each of the generic core module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating better health-related quality of life. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
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 this outcome measure for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: School functioning score | 2.73 units on a scale | Standard Deviation 18.49 |
| High-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Social functioning score | -0.40 units on a scale | Standard Deviation 18.47 |
| High-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Emotional functioning score | 4.07 units on a scale | Standard Deviation 15.382 |
| High-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Physical functioning score | 0.03 units on a scale | Standard Deviation 17.088 |
| High-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Social functioning score | 61.58 units on a scale | Standard Deviation 15.825 |
| High-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Physical functioning score | 56.15 units on a scale | Standard Deviation 19.955 |
| High-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: School functioning score | 66.17 units on a scale | Standard Deviation 18.258 |
| High-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Emotional functioning score | 70.08 units on a scale | Standard Deviation 16.836 |
| Low-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: School functioning score | -2.32 units on a scale | Standard Deviation 15.462 |
| Low-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Physical functioning score | 54.96 units on a scale | Standard Deviation 20.592 |
| Low-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Physical functioning score | -3.10 units on a scale | Standard Deviation 16.55 |
| Low-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Emotional functioning score | 69.11 units on a scale | Standard Deviation 18.711 |
| Low-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Emotional functioning score | 3.39 units on a scale | Standard Deviation 18.068 |
| Low-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Social functioning score | 62.77 units on a scale | Standard Deviation 16.54 |
| Low-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Social functioning score | -1.09 units on a scale | Standard Deviation 14.268 |
| Low-Dose Ataluren | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: School functioning score | 66.16 units on a scale | Standard Deviation 16.32 |
| Placebo | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Emotional functioning score | 65.96 units on a scale | Standard Deviation 17.964 |
| Placebo | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Physical functioning score | 51.47 units on a scale | Standard Deviation 19.274 |
| Placebo | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Social functioning score | 3.71 units on a scale | Standard Deviation 14.13 |
| Placebo | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Physical functioning score | 0.23 units on a scale | Standard Deviation 23.712 |
| Placebo | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: School functioning score | 3.48 units on a scale | Standard Deviation 13.913 |
| Placebo | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Emotional functioning score | 1.21 units on a scale | Standard Deviation 17.794 |
| Placebo | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: School functioning score | 61.93 units on a scale | Standard Deviation 13.587 |
| Placebo | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Social functioning score | 55.79 units on a scale | Standard Deviation 18.269 |
Secondary
Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48
HRQL was measured via the PedsQL. The fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. The PedsQL was completed by both the participant and/or a parent/caregiver. Fatigue-specific module obtains information relating to items such as: I feel too tired to do things that I like to do; I spend a lot of time in bed; and I have trouble remembering more than one thing at a time; Each of the fatigue-specific module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating less fatigue. Total score was the sum of all items over the number of items answered on all scales. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
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 this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 | Baseline | 73.39 units on a scale | Standard Deviation 13.671 |
| High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 | Change at Week 48 | 1.97 units on a scale | Standard Deviation 13.873 |
| Low-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 | Baseline | 70.71 units on a scale | Standard Deviation 12.72 |
| Low-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 | Change at Week 48 | 1.27 units on a scale | Standard Deviation 12.095 |
| Placebo | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 | Baseline | 68.27 units on a scale | Standard Deviation 13.17 |
| Placebo | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 | Change at Week 48 | 2.51 units on a scale | Standard Deviation 12.039 |
Secondary
Change From Baseline in Participant/Caregiver-Reported Number of Daily Accidental Falls at Week 48
Number of falls was determined by daily diary records maintained by participants and/or parent/caregivers.
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 this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Participant/Caregiver-Reported Number of Daily Accidental Falls at Week 48 | Baseline | 0.40 falls/day | Standard Deviation 0.597 |
| High-Dose Ataluren | Change From Baseline in Participant/Caregiver-Reported Number of Daily Accidental Falls at Week 48 | Change at Week 48 | -0.10 falls/day | Standard Deviation 0.466 |
| Low-Dose Ataluren | Change From Baseline in Participant/Caregiver-Reported Number of Daily Accidental Falls at Week 48 | Baseline | 0.27 falls/day | Standard Deviation 0.48 |
| Low-Dose Ataluren | Change From Baseline in Participant/Caregiver-Reported Number of Daily Accidental Falls at Week 48 | Change at Week 48 | -0.06 falls/day | Standard Deviation 0.501 |
| Placebo | Change From Baseline in Participant/Caregiver-Reported Number of Daily Accidental Falls at Week 48 | Baseline | 0.54 falls/day | Standard Deviation 0.943 |
| Placebo | Change From Baseline in Participant/Caregiver-Reported Number of Daily Accidental Falls at Week 48 | Change at Week 48 | 0.20 falls/day | Standard Deviation 1.282 |
Secondary
Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48
HRQL was measured via the PedsQL. The generic core module (including physical, emotional, social and school functioning scales) comprises 23 questions and the fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. The PedsQL was completed by both the participant and/or a parent/caregiver. Examples of items in each of the generic core module scales include: It is hard for me to run; I feel sad or blue; I cannot do things that other kids my age can do; and It is hard to pay attention in class. Each of the generic core module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating better health-related quality of life. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
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 this outcome measure for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Emotional functioning score | 2.36 units on a scale | Standard Deviation 16.742 |
| High-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: School functioning score | 67.72 units on a scale | Standard Deviation 19.276 |
| High-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Social functioning score | 5.37 units on a scale | Standard Deviation 20.463 |
| High-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: School functioning score | 3.61 units on a scale | Standard Deviation 13.008 |
| High-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Physical functioning score | 63.63 units on a scale | Standard Deviation 20.029 |
| High-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Physical functioning score | -0.94 units on a scale | Standard Deviation 19.125 |
| High-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Social functioning score | 67.50 units on a scale | Standard Deviation 21.749 |
| High-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Emotional functioning score | 73.92 units on a scale | Standard Deviation 20.418 |
| Low-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Social functioning score | 65.09 units on a scale | Standard Deviation 18.421 |
| Low-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Emotional functioning score | -1.83 units on a scale | Standard Deviation 23.725 |
| Low-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Physical functioning score | 59.27 units on a scale | Standard Deviation 22.782 |
| Low-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: School functioning score | 64.55 units on a scale | Standard Deviation 20.396 |
| Low-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Emotional functioning score | 73.70 units on a scale | Standard Deviation 20.223 |
| Low-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Social functioning score | 3.89 units on a scale | Standard Deviation 21.841 |
| Low-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: School functioning score | 6.11 units on a scale | Standard Deviation 23.765 |
| Low-Dose Ataluren | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Physical functioning score | 2.37 units on a scale | Standard Deviation 25.105 |
| Placebo | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: School functioning score | 4.06 units on a scale | Standard Deviation 23.244 |
| Placebo | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Emotional functioning score | 4.30 units on a scale | Standard Deviation 22.315 |
| Placebo | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Social functioning score | 63.36 units on a scale | Standard Deviation 20.476 |
| Placebo | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Physical functioning score | 61.87 units on a scale | Standard Deviation 19.411 |
| Placebo | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Physical functioning score | -1.00 units on a scale | Standard Deviation 24.022 |
| Placebo | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: Emotional functioning score | 70.13 units on a scale | Standard Deviation 19.332 |
| Placebo | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Change at Week 48: Social functioning score | 7.75 units on a scale | Standard Deviation 18.87 |
| Placebo | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 | Baseline: School functioning score | 64.65 units on a scale | Standard Deviation 17.841 |
Secondary
Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48
HRQL was measured via the PedsQL. The fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. PedsQL was completed by both the participant and/or a parent/caregiver. Fatigue-specific module obtains information relating to items such as: I feel too tired to do things that I like to do; I spend a lot of time in bed; and I have trouble remembering more than one thing at a time; Each of the fatigue-specific module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating less fatigue. Total score was the sum of all items over the number of items answered on all scales. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
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 this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 | Baseline | 69.47 units on a scale | Standard Deviation 16.525 |
| High-Dose Ataluren | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 | Change at Week 48 | 6.95 units on a scale | Standard Deviation 13.46 |
| Low-Dose Ataluren | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 | Baseline | 71.62 units on a scale | Standard Deviation 16.474 |
| Low-Dose Ataluren | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 | Change at Week 48 | 0.45 units on a scale | Standard Deviation 23.068 |
| Placebo | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 | Baseline | 69.70 units on a scale | Standard Deviation 15.263 |
| Placebo | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 | Change at Week 48 | 3.92 units on a scale | Standard Deviation 16.512 |
Secondary
Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48
SAM is a pedometer(worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again. Proportion of time during active periods spent at low activity(≤15 steps/minute), medium activity(16-30 steps/minute), and high activity(\>30 steps/minute) were computed for each participant. Mean obtained during Screening and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as first time after 3:00 AM that \>2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was \<50% of the mean active period across all days for that participant's visit.
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 this outcome measure for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Change at Week 48: Time spent at low activity | -2.06 percentage of time | Standard Deviation 7.903 |
| High-Dose Ataluren | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Baseline: Time spent at high activity | 6.59 percentage of time | Standard Deviation 4.077 |
| High-Dose Ataluren | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Change at Week 48: Time spent at medium activity | -1.35 percentage of time | Standard Deviation 3.348 |
| High-Dose Ataluren | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Baseline: Time spent at low activity | 32.91 percentage of time | Standard Deviation 7.842 |
| High-Dose Ataluren | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Change at Week 48: Time spent at high activity | -0.66 percentage of time | Standard Deviation 2.79 |
| High-Dose Ataluren | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Baseline: Time spent at medium activity | 11.11 percentage of time | Standard Deviation 4.013 |
| Low-Dose Ataluren | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Change at Week 48: Time spent at high activity | -0.96 percentage of time | Standard Deviation 2.828 |
| Low-Dose Ataluren | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Change at Week 48: Time spent at low activity | -1.12 percentage of time | Standard Deviation 8.22 |
| Low-Dose Ataluren | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Baseline: Time spent at medium activity | 10.00 percentage of time | Standard Deviation 3.656 |
| Low-Dose Ataluren | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Change at Week 48: Time spent at medium activity | -0.69 percentage of time | Standard Deviation 3.828 |
| Low-Dose Ataluren | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Baseline: Time spent at low activity | 32.38 percentage of time | Standard Deviation 8.213 |
| Low-Dose Ataluren | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Baseline: Time spent at high activity | 5.78 percentage of time | Standard Deviation 3.785 |
| Placebo | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Change at Week 48: Time spent at low activity | -1.11 percentage of time | Standard Deviation 5.586 |
| Placebo | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Baseline: Time spent at medium activity | 11.84 percentage of time | Standard Deviation 4.304 |
| Placebo | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Baseline: Time spent at low activity | 32.86 percentage of time | Standard Deviation 6.239 |
| Placebo | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Baseline: Time spent at high activity | 7.17 percentage of time | Standard Deviation 3.7 |
| Placebo | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Change at Week 48: Time spent at medium activity | -1.92 percentage of time | Standard Deviation 4.178 |
| Placebo | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 | Change at Week 48: Time spent at high activity | -1.03 percentage of time | Standard Deviation 3.783 |
Secondary
Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 48
Blood samples collected for chemistry assays were used to quantify serum CK concentrations. Serum CK was assessed as a potential biomarker for muscle fragility, with a reduction in serum CK considered to be a positive outcome.
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 this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 48 | Baseline | 10853.65 units/liter (U/L) | Standard Deviation 6251.136 |
| High-Dose Ataluren | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 48 | Change at Week 48 | -1680.09 units/liter (U/L) | Standard Deviation 4264.769 |
| Low-Dose Ataluren | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 48 | Baseline | 12084.70 units/liter (U/L) | Standard Deviation 7772.631 |
| Low-Dose Ataluren | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 48 | Change at Week 48 | -2146.32 units/liter (U/L) | Standard Deviation 7151.944 |
| Placebo | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 48 | Baseline | 10569.60 units/liter (U/L) | Standard Deviation 6488.477 |
| Placebo | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 48 | Change at Week 48 | -1235.13 units/liter (U/L) | Standard Deviation 4323.943 |
Secondary
Change From Baseline in Time to Climb 4 Stairs at Week 48
If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. 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, 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Time to Climb 4 Stairs at Week 48 | Change at Week 48 | 3.51 seconds | Standard Deviation 6.794 |
| High-Dose Ataluren | Change From Baseline in Time to Climb 4 Stairs at Week 48 | Baseline | 7.63 seconds | Standard Deviation 7.522 |
| Low-Dose Ataluren | Change From Baseline in Time to Climb 4 Stairs at Week 48 | Baseline | 6.94 seconds | Standard Deviation 6.474 |
| Low-Dose Ataluren | Change From Baseline in Time to Climb 4 Stairs at Week 48 | Change at Week 48 | 2.39 seconds | Standard Deviation 4.618 |
| Placebo | Change From Baseline in Time to Climb 4 Stairs at Week 48 | Baseline | 6.04 seconds | Standard Deviation 5.661 |
| Placebo | Change From Baseline in Time to Climb 4 Stairs at Week 48 | Change at Week 48 | 4.79 seconds | Standard Deviation 7.949 |
Secondary
Change From Baseline in Time to Descend 4 Stairs at Week 48
If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. 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, 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Time to Descend 4 Stairs at Week 48 | Baseline | 6.75 seconds | Standard Deviation 7.219 |
| High-Dose Ataluren | Change From Baseline in Time to Descend 4 Stairs at Week 48 | Change at Week 48 | 2.95 seconds | Standard Deviation 7.323 |
| Low-Dose Ataluren | Change From Baseline in Time to Descend 4 Stairs at Week 48 | Baseline | 6.08 seconds | Standard Deviation 5.985 |
| Low-Dose Ataluren | Change From Baseline in Time to Descend 4 Stairs at Week 48 | Change at Week 48 | 2.41 seconds | Standard Deviation 6.162 |
| Placebo | Change From Baseline in Time to Descend 4 Stairs at Week 48 | Baseline | 5.52 seconds | Standard Deviation 5.753 |
| Placebo | Change From Baseline in Time to Descend 4 Stairs at Week 48 | Change at Week 48 | 4.03 seconds | Standard Deviation 7.828 |
Secondary
Change From Baseline in Time to Stand From Supine Position at Week 48
If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. 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, 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Time to Stand From Supine Position at Week 48 | Baseline | 12.25 seconds | Standard Deviation 11.191 |
| High-Dose Ataluren | Change From Baseline in Time to Stand From Supine Position at Week 48 | Change at Week 48 | 3.00 seconds | Standard Deviation 5.686 |
| Low-Dose Ataluren | Change From Baseline in Time to Stand From Supine Position at Week 48 | Baseline | 10.80 seconds | Standard Deviation 9.924 |
| Low-Dose Ataluren | Change From Baseline in Time to Stand From Supine Position at Week 48 | Change at Week 48 | 3.23 seconds | Standard Deviation 5.761 |
| Placebo | Change From Baseline in Time to Stand From Supine Position at Week 48 | Baseline | 11.50 seconds | Standard Deviation 11.44 |
| Placebo | Change From Baseline in Time to Stand From Supine Position at Week 48 | Change at Week 48 | 3.24 seconds | Standard Deviation 7.253 |
Secondary
Change From Baseline in Time to Walk/Run 10 Meters at Week 48
If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. 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, 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Change From Baseline in Time to Walk/Run 10 Meters at Week 48 | Baseline | 7.80 seconds | Standard Deviation 5.243 |
| High-Dose Ataluren | Change From Baseline in Time to Walk/Run 10 Meters at Week 48 | Change at Week 48 | 2.37 seconds | Standard Deviation 6.149 |
| Low-Dose Ataluren | Change From Baseline in Time to Walk/Run 10 Meters at Week 48 | Baseline | 7.45 seconds | Standard Deviation 4.373 |
| Low-Dose Ataluren | Change From Baseline in Time to Walk/Run 10 Meters at Week 48 | Change at Week 48 | 1.68 seconds | Standard Deviation 5.617 |
| Placebo | Change From Baseline in Time to Walk/Run 10 Meters at Week 48 | Baseline | 6.86 seconds | Standard Deviation 2.813 |
| Placebo | Change From Baseline in Time to Walk/Run 10 Meters at Week 48 | Change at Week 48 | 3.03 seconds | Standard Deviation 6.691 |
Secondary
Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score
TSQM consisted of 14 questions about treatment satisfaction with drug in 4 domains: Effectiveness (Questions 1-3 scored as 1 \[extremely dissatisfied\] to 7 \[extremely satisfied\]), Side Effects (question 4 scored as 0 \[no\] or 1 \[yes\]; question 5 scored as 1 \[extremely bothersome\] to 5 \[not at all bothersome\]; questions 6 - 8 scored as 1 \[a great deal\] to 5 \[not at all\]), Convenience (questions 9 and 10 scored as 1 \[extremely difficult\] to 7 \[extremely easy\]; question 11 scored as 1 \[extremely inconvenient\] to 5 \[extremely convenient\]) and Global Satisfaction (question 12 scored as 1 \[not at all confident\] to 7 \[extremely confident\]; question 13 scored as 1 \[not at all certain\] to 5 \[extremely certain\]; question 14 scored as 1 \[extremely dissatisfied\] to 5 \[extremely satisfied\]). The scores of each of the domains were added together and an algorithm was used to create a score of 0 to 100, with higher scores indicating better treatment satisfaction.
Time frame: 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 this outcome measure for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score | Effectiveness score | 55.97 units on a scale | Standard Deviation 27.796 |
| High-Dose Ataluren | Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score | Side-effects score | 96.36 units on a scale | Standard Deviation 11.199 |
| High-Dose Ataluren | Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score | Convenience score | 55.85 units on a scale | Standard Deviation 17.008 |
| High-Dose Ataluren | Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score | Global satisfaction score | 61.04 units on a scale | Standard Deviation 25.967 |
| Low-Dose Ataluren | Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score | Global satisfaction score | 61.19 units on a scale | Standard Deviation 23.691 |
| Low-Dose Ataluren | Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score | Effectiveness score | 54.60 units on a scale | Standard Deviation 22.307 |
| Low-Dose Ataluren | Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score | Convenience score | 58.23 units on a scale | Standard Deviation 19.04 |
| Low-Dose Ataluren | Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score | Side-effects score | 97.77 units on a scale | Standard Deviation 7.578 |
| Placebo | Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score | Global satisfaction score | 57.56 units on a scale | Standard Deviation 21.851 |
| Placebo | Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score | Side-effects score | 96.89 units on a scale | Standard Deviation 8.874 |
| Placebo | Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score | Convenience score | 60.91 units on a scale | Standard Deviation 16.665 |
| Placebo | Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score | Effectiveness score | 51.26 units on a scale | Standard Deviation 23.536 |
Secondary
Percent Change From Pre-Treatment Visit (1 Week Prior to Baseline Visit) in Biceps Muscle Dystrophin Expression at Post-Treatment Visit (Week 36), as Determined by Immunofluorescence
Immunofluorescence evidence of a change in dystrophin expression on biceps muscle biopsy was defined as an increase in the staining of the sarcolemmal membrane with an antibody to the C-terminal portion of the dystrophin protein (excluding revertant fibers) between the pre-treatment (1 week prior to Baseline visit) and post-treatment (Week 36) biopsies. The biceps muscle was biopsied from one arm for confirmation of the absence or reduced levels of dystrophin prior to treatment initiation and from the other arm to assess for production of dystrophin post-treatment.
Time frame: Pre-Treatment (1 week prior to baseline), post-treatment (Week 36)
Population: As-treated population included all randomized participants who actually received any study treatment. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren | Percent Change From Pre-Treatment Visit (1 Week Prior to Baseline Visit) in Biceps Muscle Dystrophin Expression at Post-Treatment Visit (Week 36), as Determined by Immunofluorescence | Pre-treatment | 336.096 percent change | Standard Deviation 138.9753 |
| High-Dose Ataluren | Percent Change From Pre-Treatment Visit (1 Week Prior to Baseline Visit) in Biceps Muscle Dystrophin Expression at Post-Treatment Visit (Week 36), as Determined by Immunofluorescence | Percent change post-treatment | -1.278 percent change | Standard Deviation 27.7432 |
| Low-Dose Ataluren | Percent Change From Pre-Treatment Visit (1 Week Prior to Baseline Visit) in Biceps Muscle Dystrophin Expression at Post-Treatment Visit (Week 36), as Determined by Immunofluorescence | Pre-treatment | 359.797 percent change | Standard Deviation 142.7361 |
| Low-Dose Ataluren | Percent Change From Pre-Treatment Visit (1 Week Prior to Baseline Visit) in Biceps Muscle Dystrophin Expression at Post-Treatment Visit (Week 36), as Determined by Immunofluorescence | Percent change post-treatment | -2.128 percent change | Standard Deviation 28.8287 |
| Placebo | Percent Change From Pre-Treatment Visit (1 Week Prior to Baseline Visit) in Biceps Muscle Dystrophin Expression at Post-Treatment Visit (Week 36), as Determined by Immunofluorescence | Pre-treatment | 357.271 percent change | Standard Deviation 139.665 |
| Placebo | Percent Change From Pre-Treatment Visit (1 Week Prior to Baseline Visit) in Biceps Muscle Dystrophin Expression at Post-Treatment Visit (Week 36), as Determined by Immunofluorescence | Percent change post-treatment | -0.898 percent change | Standard Deviation 19.2112 |
Other Pre-specified
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) |
|---|---|---|
| High-Dose Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (AEs) | 95.0 percentage of participants |
| Low-Dose Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (AEs) | 96.5 percentage of participants |
| Placebo | Percentage of Participants With Treatment-Emergent Adverse Events (AEs) | 98.2 percentage of participants |
Other Pre-specified
Study Drug Compliance
Study drug compliance was assessed by participant daily diary and 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 (MEDIAN) |
|---|---|---|
| High-Dose Ataluren | Study Drug Compliance | 97.87 percentage of drug |
| Low-Dose Ataluren | Study Drug Compliance | 97.03 percentage of drug |
| Placebo | Study Drug Compliance | 97.74 percentage of drug |