Becker Muscular Dystrophy, Duchenne Muscular Dystrophy
Conditions
Keywords
Duchenne muscular dystrophy, Becker muscular dystrophy, Nonsense mutation, Premature stop codon, DMD, BMD, Ataluren, PTC124
Brief summary
Duchenne/Becker muscular dystrophy (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 10-15% of boys with the disease. Ataluren (PTC124) is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2b extension trial that will evaluate the long-term safety of ataluren (PTC124) in boys with nonsense mutation DMD/BMD, as determined by adverse events and laboratory abnormalities. The study will also assess changes in walking, muscle function, and other important clinical and laboratory measures.
Detailed description
This is a Phase 2b, international, multicenter, open-label extension study for participants who successfully completed blinded study drug in Study 007. This extension study will evaluate the long-term administration of ataluren administered 3 times per day (TID) at morning, midday, and evening doses of 20, 20, and 40 milligrams/kilogram (mg/kg), respectively, in participants with nonsense mutation Duchenne/Becker muscular dystrophy (nmDBMD).
Interventions
DRUGAtaluren
Ataluren oral powder for suspension will be administered as per dose and schedule specified in the arm.
Sponsors
Genzyme, a Sanofi Company
PTC Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completion of blinded study drug treatment in the previous Phase 2b study (PTC124-GD-007-DMD). * Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if less than \[\<\]18 years of age). * In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during PTC124 administration and the 6-week follow up period. * Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.
Exclusion criteria
* 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). * Ongoing participation in any other therapeutic clinical trial. * Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the subject, 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 |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (AEs) | Baseline (Week 48 of Study 007) up to Week 102 | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of an AE was classified as: mild (does not interfere with usual function), moderate (interferes to some extent with usual function) and severe (interferes significantly with usual function). Drug-related AEs: AEs with a possible or probable relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention. TEAE: AE that occurred or worsened in the period extending from first dose of study drug in this study to 6 weeks after last dose of study drug in this study. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Number of Participants With Clinically Significant Abnormal Laboratory Parameters | Baseline (Week 48 of Study 007) up to Week 102 | Laboratory parameters tests included hematology, biochemistry assay (hepatic, renal, and serum electrolyte values), adrenal assays, and urinalysis. Clinical significance was defined as per investigator's judgement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 60, as Assessed by SAM | Baseline (Week 48 of Study 007), Week 60 | 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. 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 60, as Assessed by SAM | Baseline (Week 48 of Study 007), Week 60 | 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. 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 60, as Assessed by SAM | Baseline (Week 48 of Study 007), Week 60 | 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. 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 Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline (Week 48 of Study 007), Week 60 | 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 SAM for at least 9 consecutive days. SAM was used to record number of strides/minute following each visit. A stride is leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again. Percentage of time during active periods spent at no activity (0 steps/min), low activity (≤15 steps/min), medium activity (16-30 steps/min), and high activity (\>30 steps/min) were computed for each participant. 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 Time to Stand From Supine Position at Week 60 | Baseline (Week 48 of Study 007), Week 60 | 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 60 | Baseline (Week 48 of Study 007), Week 60 | 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 60 | Baseline (Week 48 of Study 007), Week 60 | 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 60 | Baseline (Week 48 of Study 007), Week 60 | 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 Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline (Week 48 of Study 007), Week 60 | 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. |
| Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 60 | Baseline (Week 48 of Study 007), Week 60 | 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. |
| 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 60 | Baseline (Week 48 of Study 007), Week 60 | 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 60. |
| Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 60 | Baseline (Week 48 of Study 007), Week 60 | 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 60 | Baseline (Week 48 of Study 007), Week 60 | 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 60. |
| Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Baseline (Week 48 of Study 007), Week 60 | 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 60. |
| Change From Baseline in Participant and Parent/Caregiver Reported Activities of Daily Living of Participants Who Were Unable to Complete the 6MWT (Nonambulatory Participants), as Measured by the Egen Klassifikation (EK) Scale at Week 60 | Baseline (Week 48 of Study 007), Week 60 | Activities of daily living were measured using the EK scale in all participants who were unable to complete the 6MWT at Screening/Baseline on Day 1. The EK scale is an ordinal scale ranging from 0 to 30 points where 0 represents the highest level of independent function and 30 the lowest. The scale consists of 10 categories (each scored 0 to 3), involving different functional domains including 1) ability to use wheelchair, 2) ability to transfer from wheelchair, 3) ability to stand, 4) ability to balance in the wheelchair, 5) ability to move the arms, 6) ability to use the hands and arms when eating, 7) ability to turn in bed, 8) ability to cough, 9) ability to speak, and 10) physical well-being. The administration of the EK scale consisted of an interview of the participant to capture how he performed the tasks of daily life (as described by Categories 1 to 9) and how he perceived his well-being (as described by Category 10). |
| Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline (Week 48 of Study 007), Week 60 | 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 Serum Concentration of Creatine Kinase (CK) at Week 60 | Baseline (Week 48 of Study 007), Week 60 | 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. |
| Study Drug Compliance | Baseline (Week 48 of Study 007) to Week 96 | 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. |
| Trough Ataluren Plasma Concentration | Pre-morning dose (0 hour) at Baseline (Week 48 of 007 study), Weeks 54, 60, 72, 84, and 96 | Plasma samples for the determination of ataluren concentrations were analyzed at the bioanalytical laboratory for ataluren parent drug using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC/MS-MS) method with a lower limit of quantitation (LLOQ) of 0.5 micrograms/millilitre (mcg/mL). Values below the LLOQ were set to 0. |
| Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Baseline (Week 48 of Study 007), Week 60 | 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 Mean Activity Period/Day/Visit at Week 60, as Assessed by Step Activity Monitoring (SAM) | Baseline (Week 48 of Study 007), Week 60 | 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. 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. |
Countries
Australia, Belgium, Canada, France, Germany, Israel, Italy, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
A total of 173 participants were screened for eligibility to enter this extension study after completing the 48-week double-blind study PTC124-GD-007-DMD (NCT00592553). All participants met entry criteria and enrolled in this study.
Pre-assignment details
Participants were categorized by the treatment group to which they had been randomly assigned in Study PTC124-GD-007-DMD (NCT00592553).
Participants by arm
| Arm | Count |
|---|---|
| High-Dose Ataluren/High-Dose Ataluren Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive 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 up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | 59 |
| Low-Dose Ataluren/High-Dose Ataluren Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, 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 up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | 57 |
| Placebo/High-Dose Ataluren Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, 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 up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | 57 |
| Total | 173 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Study terminated by Sponsor | 59 | 57 | 57 |
Baseline characteristics
| Characteristic | Low-Dose Ataluren/High-Dose Ataluren | High-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Total |
|---|---|---|---|---|
| Age, Continuous | 9.7 years STANDARD_DEVIATION 2.89 | 9.4 years STANDARD_DEVIATION 2.53 | 9.3 years STANDARD_DEVIATION 2.28 | 9.5 years STANDARD_DEVIATION 2.57 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 57 Participants | 59 Participants | 57 Participants | 173 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 53 / 59 | 51 / 57 | 51 / 57 | 155 / 173 |
| serious Total, serious adverse events | 0 / 59 | 1 / 57 | 2 / 57 | 3 / 173 |
Outcome results
Primary
Number of Participants With Clinically Significant Abnormal Laboratory Parameters
Laboratory parameters tests included hematology, biochemistry assay (hepatic, renal, and serum electrolyte values), adrenal assays, and urinalysis. Clinical significance was defined as per investigator's judgement.
Time frame: Baseline (Week 48 of Study 007) up to Week 102
Population: As-treated population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Number of Participants With Clinically Significant Abnormal Laboratory Parameters | 0 Participants |
| Low-Dose Ataluren/High-Dose Ataluren | Number of Participants With Clinically Significant Abnormal Laboratory Parameters | 0 Participants |
| Placebo/High-Dose Ataluren | Number of Participants With Clinically Significant Abnormal Laboratory Parameters | 0 Participants |
| Overall Participants: High-Dose Ataluren | Number of Participants With Clinically Significant Abnormal Laboratory Parameters | 0 Participants |
Primary
Number 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. Severity of an AE was classified as: mild (does not interfere with usual function), moderate (interferes to some extent with usual function) and severe (interferes significantly with usual function). Drug-related AEs: AEs with a possible or probable relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention. TEAE: AE that occurred or worsened in the period extending from first dose of study drug in this study to 6 weeks after last dose of study drug in this study. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline (Week 48 of Study 007) up to Week 102
Population: As-treated population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Any AEs | 52 Participants |
| High-Dose Ataluren/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Drug-related AEs | 10 Participants |
| High-Dose Ataluren/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Serious AEs | 0 Participants |
| High-Dose Ataluren/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Mild AEs | 34 Participants |
| High-Dose Ataluren/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Moderate AEs | 13 Participants |
| High-Dose Ataluren/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Severe AEs | 5 Participants |
| Low-Dose Ataluren/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Severe AEs | 4 Participants |
| Low-Dose Ataluren/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Mild AEs | 23 Participants |
| Low-Dose Ataluren/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Any AEs | 49 Participants |
| Low-Dose Ataluren/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Serious AEs | 1 Participants |
| Low-Dose Ataluren/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Drug-related AEs | 10 Participants |
| Low-Dose Ataluren/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Moderate AEs | 22 Participants |
| Placebo/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Drug-related AEs | 22 Participants |
| Placebo/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Serious AEs | 2 Participants |
| Placebo/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Mild AEs | 26 Participants |
| Placebo/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Severe AEs | 3 Participants |
| Placebo/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Moderate AEs | 19 Participants |
| Placebo/High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Any AEs | 48 Participants |
| Overall Participants: High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Moderate AEs | 54 Participants |
| Overall Participants: High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Severe AEs | 12 Participants |
| Overall Participants: High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Drug-related AEs | 42 Participants |
| Overall Participants: High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Mild AEs | 83 Participants |
| Overall Participants: High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Any AEs | 149 Participants |
| Overall Participants: High-Dose Ataluren | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Serious AEs | 3 Participants |
Secondary
Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 60
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 of Study 007), Week 60
Population: Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 60 | Baseline | 351.60 meters | Standard Deviation 130.312 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 60 | Change at Week 60 | -17.23 meters | Standard Deviation 39.608 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 60 | Change at Week 60 | -10.50 meters | Standard Deviation 41.39 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 60 | Baseline | 375.95 meters | Standard Deviation 98.976 |
| Placebo/High-Dose Ataluren | Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 60 | Baseline | 356.25 meters | Standard Deviation 109.369 |
| Placebo/High-Dose Ataluren | Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 60 | Change at Week 60 | -7.06 meters | Standard Deviation 50.121 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 60 | Baseline | 361.11 meters | Standard Deviation 113.76 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 60 | Change at Week 60 | -11.56 meters | Standard Deviation 43.881 |
Secondary
Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, 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 of Study 007), Week 60
Population: Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Resting heart rate | 105.3 beats/minute | Standard Deviation 13.29 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 60: Resting heart rate | 4.0 beats/minute | Standard Deviation 13.91 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Active heart rate | 138.7 beats/minute | Standard Deviation 21.45 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 60: Active heart rate | 1.6 beats/minute | Standard Deviation 17.65 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Recovery heart rate | 110.0 beats/minute | Standard Deviation 13.32 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 60: Recovery heart rate | 2.1 beats/minute | Standard Deviation 12.82 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 60: Recovery heart rate | 4.6 beats/minute | Standard Deviation 12.57 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 60: Active heart rate | 6.1 beats/minute | Standard Deviation 15.45 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Resting heart rate | 108.8 beats/minute | Standard Deviation 10.71 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Active heart rate | 144.8 beats/minute | Standard Deviation 14.55 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 60: Resting heart rate | 3.7 beats/minute | Standard Deviation 10.11 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Recovery heart rate | 112.0 beats/minute | Standard Deviation 12.17 |
| Placebo/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 60: Resting heart rate | 4.8 beats/minute | Standard Deviation 10.82 |
| Placebo/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Active heart rate | 138.6 beats/minute | Standard Deviation 20.87 |
| Placebo/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 60: Active heart rate | 2.4 beats/minute | Standard Deviation 14.87 |
| Placebo/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 60: Recovery heart rate | 2.3 beats/minute | Standard Deviation 11.29 |
| Placebo/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Recovery heart rate | 109.4 beats/minute | Standard Deviation 13.21 |
| Placebo/High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Resting heart rate | 103.7 beats/minute | Standard Deviation 12.98 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Recovery heart rate | 110.4 beats/minute | Standard Deviation 12.88 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 60: Recovery heart rate | 3.0 beats/minute | Standard Deviation 12.2 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 60: Resting heart rate | 4.2 beats/minute | Standard Deviation 11.65 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Change at Week 60: Active heart rate | 3.4 beats/minute | Standard Deviation 16.07 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Resting heart rate | 105.9 beats/minute | Standard Deviation 12.48 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 | Baseline: Active heart rate | 140.6 beats/minute | Standard Deviation 19.36 |
Secondary
Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, 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. 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 of Study 007), Week 60
Population: Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 10-minute total step count | -1.140 steps | Standard Deviation 6.9584 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 60-minute total step count | -0.977 steps | Standard Deviation 3.7328 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 20-minute total step count | 28.138 steps | Standard Deviation 11.0629 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 20-minute total step count | -1.459 steps | Standard Deviation 6.7165 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 30-minute total step count | 24.222 steps | Standard Deviation 9.9576 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 10-minute total step count | 34.603 steps | Standard Deviation 12.4886 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 30-minute total step count | -1.400 steps | Standard Deviation 5.7605 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 60-minute total step count | 18.019 steps | Standard Deviation 7.8145 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 20-minute total step count | -0.662 steps | Standard Deviation 6.2171 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 60-minute total step count | 16.453 steps | Standard Deviation 5.6625 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 20-minute total step count | 26.096 steps | Standard Deviation 7.9168 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 10-minute total step count | -0.607 steps | Standard Deviation 7.2946 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 30-minute total step count | 22.205 steps | Standard Deviation 7.1045 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 60-minute total step count | -0.210 steps | Standard Deviation 4.7035 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 30-minute total step count | -0.450 steps | Standard Deviation 5.6811 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 10-minute total step count | 32.863 steps | Standard Deviation 8.8533 |
| Placebo/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 10-minute total step count | -2.372 steps | Standard Deviation 7.1735 |
| Placebo/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 30-minute total step count | 24.498 steps | Standard Deviation 8.4938 |
| Placebo/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 20-minute total step count | 28.323 steps | Standard Deviation 9.3133 |
| Placebo/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 20-minute total step count | -2.510 steps | Standard Deviation 6.4346 |
| Placebo/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 10-minute total step count | 35.256 steps | Standard Deviation 10.0379 |
| Placebo/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 30-minute total step count | -2.457 steps | Standard Deviation 5.9579 |
| Placebo/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 60-minute total step count | 18.599 steps | Standard Deviation 6.9509 |
| Placebo/High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 60-minute total step count | -2.257 steps | Standard Deviation 5.1038 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 60-minute total step count | -1.162 steps | Standard Deviation 4.5803 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 10-minute total step count | 34.241 steps | Standard Deviation 10.5911 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 10-minute total step count | -1.384 steps | Standard Deviation 7.117 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 20-minute total step count | -1.558 steps | Standard Deviation 6.4549 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 30-minute total step count | 23.648 steps | Standard Deviation 8.6306 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Change at Week 60: 30-minute total step count | -1.452 steps | Standard Deviation 5.811 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 60-minute total step count | 17.691 steps | Standard Deviation 6.8991 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM | Baseline: 20-minute total step count | 27.526 steps | Standard Deviation 9.5426 |
Secondary
Change From Baseline in Mean Activity Period/Day/Visit at Week 60, 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. 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 of Study 007), Week 60
Population: Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Mean Activity Period/Day/Visit at Week 60, as Assessed by Step Activity Monitoring (SAM) | Baseline | 759.715 meters | Standard Deviation 77.521 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Mean Activity Period/Day/Visit at Week 60, as Assessed by Step Activity Monitoring (SAM) | Change at Week 60 | 1.946 meters | Standard Deviation 61.2247 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Mean Activity Period/Day/Visit at Week 60, as Assessed by Step Activity Monitoring (SAM) | Change at Week 60 | 34.283 meters | Standard Deviation 88.1587 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Mean Activity Period/Day/Visit at Week 60, as Assessed by Step Activity Monitoring (SAM) | Baseline | 742.223 meters | Standard Deviation 107.7264 |
| Placebo/High-Dose Ataluren | Change From Baseline in Mean Activity Period/Day/Visit at Week 60, as Assessed by Step Activity Monitoring (SAM) | Baseline | 747.464 meters | Standard Deviation 102.6531 |
| Placebo/High-Dose Ataluren | Change From Baseline in Mean Activity Period/Day/Visit at Week 60, as Assessed by Step Activity Monitoring (SAM) | Change at Week 60 | -1.866 meters | Standard Deviation 93.0531 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Mean Activity Period/Day/Visit at Week 60, as Assessed by Step Activity Monitoring (SAM) | Baseline | 750.016 meters | Standard Deviation 96.1057 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Mean Activity Period/Day/Visit at Week 60, as Assessed by Step Activity Monitoring (SAM) | Change at Week 60 | 10.991 meters | Standard Deviation 82.6356 |
Secondary
Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 60, 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. 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 of Study 007), Week 60
Population: Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 60, as Assessed by SAM | Baseline | 4934.575 steps | Standard Deviation 2433.23 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 60, as Assessed by SAM | Change at Week 60 | -357.679 steps | Standard Deviation 1232.109 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 60, as Assessed by SAM | Change at Week 60 | -215.062 steps | Standard Deviation 1761.773 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 60, as Assessed by SAM | Baseline | 4543.766 steps | Standard Deviation 2051.3 |
| Placebo/High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 60, as Assessed by SAM | Baseline | 5175.330 steps | Standard Deviation 2307.436 |
| Placebo/High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 60, as Assessed by SAM | Change at Week 60 | -647.504 steps | Standard Deviation 1680.522 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 60, as Assessed by SAM | Baseline | 4883.613 steps | Standard Deviation 2272.108 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 60, as Assessed by SAM | Change at Week 60 | -409.558 steps | Standard Deviation 1566.386 |
Secondary
Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 60, 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. 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 of Study 007), Week 60
Population: Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 60, as Assessed by SAM | Baseline | 395.491 steps | Standard Deviation 200.7671 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 60, as Assessed by SAM | Change at Week 60 | -27.650 steps | Standard Deviation 87.8797 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 60, as Assessed by SAM | Change at Week 60 | -34.693 steps | Standard Deviation 128.0609 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 60, as Assessed by SAM | Baseline | 368.672 steps | Standard Deviation 155.6648 |
| Placebo/High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 60, as Assessed by SAM | Baseline | 420.684 steps | Standard Deviation 188.9124 |
| Placebo/High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 60, as Assessed by SAM | Change at Week 60 | -54.755 steps | Standard Deviation 122.4142 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 60, as Assessed by SAM | Baseline | 394.787 steps | Standard Deviation 183.0994 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 60, as Assessed by SAM | Change at Week 60 | -39.010 steps | Standard Deviation 113.3481 |
Secondary
Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60
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 of Study 007), Week 60
Population: Evaluable population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, who had sufficient baseline and on-treatment data in Study 007e to assess the measure of interest. 'Number analyzed'=participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Baseline: Forward condition | 4.1 z-score | Standard Deviation 2.97 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Change at Week 60: Forward condition | 0.0 z-score | Standard Deviation 1.53 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Baseline: Backward condition | 1.4 z-score | Standard Deviation 0.98 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Change at Week 60: Backward condition | 0.1 z-score | Standard Deviation 0.86 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Change at Week 60: Forward condition | 0.0 z-score | Standard Deviation 1.19 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Baseline: Backward condition | 1.3 z-score | Standard Deviation 0.82 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Change at Week 60: Backward condition | -0.1 z-score | Standard Deviation 0.66 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Baseline: Forward condition | 3.6 z-score | Standard Deviation 2.54 |
| Placebo/High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Baseline: Backward condition | 1.2 z-score | Standard Deviation 0.66 |
| Placebo/High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Change at Week 60: Forward condition | 0.0 z-score | Standard Deviation 1.22 |
| Placebo/High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Change at Week 60: Backward condition | 0.0 z-score | Standard Deviation 0.58 |
| Placebo/High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Baseline: Forward condition | 3.2 z-score | Standard Deviation 2.21 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Change at Week 60: Backward condition | 0.0 z-score | Standard Deviation 0.71 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Change at Week 60: Forward condition | 0.0 z-score | Standard Deviation 1.32 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Baseline: Forward condition | 3.6 z-score | Standard Deviation 2.61 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 | Baseline: Backward condition | 1.3 z-score | Standard Deviation 0.84 |
Secondary
Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 60
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 of Study 007), Week 60
Population: Evaluable population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, who had sufficient baseline and on-treatment data in Study 007e to assess the measure of interest. 'Number analyzed'=participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/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 60 | Baseline: Physical functioning score | 56.8217 units on a scale | Standard Deviation 23.80718 |
| High-Dose Ataluren/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 60 | Change at Week 60: Physical functioning score | -0.8499 units on a scale | Standard Deviation 12.75478 |
| High-Dose Ataluren/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 60 | Baseline: Emotional functioning score | 74.7368 units on a scale | Standard Deviation 17.7387 |
| High-Dose Ataluren/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 60 | Change at Week 60: Emotional functioning score | -1.9231 units on a scale | Standard Deviation 11.11289 |
| High-Dose Ataluren/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 60 | Baseline: Social functioning score | 61.9518 units on a scale | Standard Deviation 19.07606 |
| High-Dose Ataluren/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 60 | Change at Week 60: Social functioning score | 1.5144 units on a scale | Standard Deviation 13.03356 |
| High-Dose Ataluren/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 60 | Baseline: School functioning score | 68.6607 units on a scale | Standard Deviation 16.05363 |
| High-Dose Ataluren/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 60 | Change at Week 60: School functioning score | 0.8000 units on a scale | Standard Deviation 9.6023 |
| Low-Dose Ataluren/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 60 | Change at Week 60: Social functioning score | -0.7908 units on a scale | Standard Deviation 11.34994 |
| Low-Dose Ataluren/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 60 | Baseline: Social functioning score | 61.6136 units on a scale | Standard Deviation 15.44605 |
| Low-Dose Ataluren/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 60 | Change at Week 60: Physical functioning score | -1.1662 units on a scale | Standard Deviation 13.27447 |
| Low-Dose Ataluren/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 60 | Change at Week 60: School functioning score | 1.6667 units on a scale | Standard Deviation 10.93177 |
| Low-Dose Ataluren/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 60 | Baseline: School functioning score | 64.0000 units on a scale | Standard Deviation 15.07389 |
| Low-Dose Ataluren/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 60 | Change at Week 60: Emotional functioning score | -0.3061 units on a scale | Standard Deviation 13.32323 |
| Low-Dose Ataluren/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 60 | Baseline: Emotional functioning score | 72.5455 units on a scale | Standard Deviation 16.04025 |
| Low-Dose Ataluren/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 60 | Baseline: Physical functioning score | 52.5162 units on a scale | Standard Deviation 20.02845 |
| Placebo/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 60 | Baseline: School functioning score | 65.9091 units on a scale | Standard Deviation 18.20894 |
| Placebo/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 60 | Baseline: Emotional functioning score | 68.2813 units on a scale | Standard Deviation 22.05309 |
| Placebo/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 60 | Change at Week 60: Emotional functioning score | -1.9213 units on a scale | Standard Deviation 16.86642 |
| Placebo/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 60 | Baseline: Social functioning score | 59.7545 units on a scale | Standard Deviation 21.34593 |
| Placebo/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 60 | Change at Week 60: Social functioning score | 0.3472 units on a scale | Standard Deviation 12.76238 |
| Placebo/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 60 | Change at Week 60: School functioning score | -1.0377 units on a scale | Standard Deviation 12.60946 |
| Placebo/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 60 | Baseline: Physical functioning score | 52.6307 units on a scale | Standard Deviation 24.35727 |
| Placebo/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 60 | Change at Week 60: Physical functioning score | -0.1736 units on a scale | Standard Deviation 14.75049 |
| Overall Participants: 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 60 | Baseline: Emotional functioning score | 71.8676 units on a scale | Standard Deviation 18.87211 |
| Overall Participants: 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 60 | Change at Week 60: Emotional functioning score | -1.4113 units on a scale | Standard Deviation 13.95342 |
| Overall Participants: 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 60 | Change at Week 60: Physical functioning score | -0.7143 units on a scale | Standard Deviation 13.55924 |
| Overall Participants: 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 60 | Baseline: Physical functioning score | 54.0152 units on a scale | Standard Deviation 22.78661 |
| Overall Participants: 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 60 | Baseline: Social functioning score | 61.1086 units on a scale | Standard Deviation 18.713 |
| Overall Participants: 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 60 | Change at Week 60: School functioning score | 0.4305 units on a scale | Standard Deviation 11.13464 |
| Overall Participants: 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 60 | Baseline: School functioning score | 66.2048 units on a scale | Standard Deviation 16.50694 |
| Overall Participants: 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 60 | Change at Week 60: Social functioning score | 0.3790 units on a scale | Standard Deviation 12.38287 |
Secondary
Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60
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 60.
Time frame: Baseline (Week 48 of Study 007), Week 60
Population: Evaluable population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, who had sufficient baseline and on-treatment data in Study 007e to assess the measure of interest. 'Number analyzed'=participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Baseline | 75.7864 units on a scale | Standard Deviation 13.88014 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Change at Week 60 | -0.3272 units on a scale | Standard Deviation 6.64218 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Change at Week 60 | 1.2219 units on a scale | Standard Deviation 10.11693 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Baseline | 71.6596 units on a scale | Standard Deviation 12.78488 |
| Placebo/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Baseline | 71.1062 units on a scale | Standard Deviation 13.62739 |
| Placebo/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Change at Week 60 | 0.2269 units on a scale | Standard Deviation 8.5513 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Baseline | 72.8724 units on a scale | Standard Deviation 13.53355 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Change at Week 60 | 0.3341 units on a scale | Standard Deviation 8.44319 |
Secondary
Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60
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: Baseline (Week 48 of Study 007), Week 60
Population: Evaluable population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, who had sufficient baseline and on-treatment data in Study 007e to assess the measure of interest. 'Number analyzed'=participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Effectiveness score | 56.8134 units on a scale | Standard Deviation 26.72451 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Effectiveness score | 2.7778 units on a scale | Standard Deviation 15.52191 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Side-effects score | 96.8182 units on a scale | Standard Deviation 10.81681 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Side-effects score | 0.7353 units on a scale | Standard Deviation 12.16084 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Convenience score | 57.4074 units on a scale | Standard Deviation 16.10609 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Convenience score | 0.8386 units on a scale | Standard Deviation 12.39372 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Global satisfaction score | 61.4286 units on a scale | Standard Deviation 25.95857 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Global satisfaction score | -0.2695 units on a scale | Standard Deviation 13.57882 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Convenience score | -1.6548 units on a scale | Standard Deviation 11.75175 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Convenience score | 57.9798 units on a scale | Standard Deviation 19.05889 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Effectiveness score | 5.6159 units on a scale | Standard Deviation 19.53233 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Global satisfaction score | 1.2538 units on a scale | Standard Deviation 15.30213 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Global satisfaction score | 60.4870 units on a scale | Standard Deviation 23.30835 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Side-effects score | -1.0638 units on a scale | Standard Deviation 7.745 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Side-effects score | 97.7273 units on a scale | Standard Deviation 7.64176 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Effectiveness score | 53.8580 units on a scale | Standard Deviation 21.53292 |
| Placebo/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Global satisfaction score | 56.7791 units on a scale | Standard Deviation 21.25768 |
| Placebo/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Side-effects score | 96.8364 units on a scale | Standard Deviation 8.94695 |
| Placebo/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Side-effects score | -1.2587 units on a scale | Standard Deviation 10.84441 |
| Placebo/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Convenience score | 60.5967 units on a scale | Standard Deviation 16.65858 |
| Placebo/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Convenience score | 1.3333 units on a scale | Standard Deviation 9.80472 |
| Placebo/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Global satisfaction score | -0.4643 units on a scale | Standard Deviation 14.78188 |
| Placebo/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Effectiveness score | 50.4274 units on a scale | Standard Deviation 22.96804 |
| Placebo/High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Effectiveness score | 1.7778 units on a scale | Standard Deviation 14.99307 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Side-effects score | 97.1291 units on a scale | Standard Deviation 9.18246 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Side-effects score | -0.4994 units on a scale | Standard Deviation 10.43907 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Effectiveness score | 3.3295 units on a scale | Standard Deviation 16.6846 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Effectiveness score | 53.7212 units on a scale | Standard Deviation 23.82541 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Convenience score | 58.6345 units on a scale | Standard Deviation 17.26216 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Global satisfaction score | 0.1429 units on a scale | Standard Deviation 14.45922 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Baseline: Global satisfaction score | 59.5819 units on a scale | Standard Deviation 23.54109 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 | Change at Week 60: Convenience score | 0.2222 units on a scale | Standard Deviation 11.38059 |
Secondary
Change From Baseline in Participant and Parent/Caregiver Reported Activities of Daily Living of Participants Who Were Unable to Complete the 6MWT (Nonambulatory Participants), as Measured by the Egen Klassifikation (EK) Scale at Week 60
Activities of daily living were measured using the EK scale in all participants who were unable to complete the 6MWT at Screening/Baseline on Day 1. The EK scale is an ordinal scale ranging from 0 to 30 points where 0 represents the highest level of independent function and 30 the lowest. The scale consists of 10 categories (each scored 0 to 3), involving different functional domains including 1) ability to use wheelchair, 2) ability to transfer from wheelchair, 3) ability to stand, 4) ability to balance in the wheelchair, 5) ability to move the arms, 6) ability to use the hands and arms when eating, 7) ability to turn in bed, 8) ability to cough, 9) ability to speak, and 10) physical well-being. The administration of the EK scale consisted of an interview of the participant to capture how he performed the tasks of daily life (as described by Categories 1 to 9) and how he perceived his well-being (as described by Category 10).
Time frame: Baseline (Week 48 of Study 007), Week 60
Population: Non-Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and who had lost all independent ambulation prior to entering Study 007e. 'Number analyzed'=participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Participant and Parent/Caregiver Reported Activities of Daily Living of Participants Who Were Unable to Complete the 6MWT (Nonambulatory Participants), as Measured by the Egen Klassifikation (EK) Scale at Week 60 | Baseline | 3.0 units on a scale | Standard Deviation 2 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Participant and Parent/Caregiver Reported Activities of Daily Living of Participants Who Were Unable to Complete the 6MWT (Nonambulatory Participants), as Measured by the Egen Klassifikation (EK) Scale at Week 60 | Change at Week 60 | 1.5 units on a scale | Standard Deviation 0.58 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Participant and Parent/Caregiver Reported Activities of Daily Living of Participants Who Were Unable to Complete the 6MWT (Nonambulatory Participants), as Measured by the Egen Klassifikation (EK) Scale at Week 60 | Change at Week 60 | 0.8 units on a scale | Standard Deviation 1.26 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Participant and Parent/Caregiver Reported Activities of Daily Living of Participants Who Were Unable to Complete the 6MWT (Nonambulatory Participants), as Measured by the Egen Klassifikation (EK) Scale at Week 60 | Baseline | 4.3 units on a scale | Standard Deviation 0.5 |
| Placebo/High-Dose Ataluren | Change From Baseline in Participant and Parent/Caregiver Reported Activities of Daily Living of Participants Who Were Unable to Complete the 6MWT (Nonambulatory Participants), as Measured by the Egen Klassifikation (EK) Scale at Week 60 | Baseline | 3.2 units on a scale | Standard Deviation 1.92 |
| Placebo/High-Dose Ataluren | Change From Baseline in Participant and Parent/Caregiver Reported Activities of Daily Living of Participants Who Were Unable to Complete the 6MWT (Nonambulatory Participants), as Measured by the Egen Klassifikation (EK) Scale at Week 60 | Change at Week 60 | -0.8 units on a scale | Standard Deviation 1.48 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Participant and Parent/Caregiver Reported Activities of Daily Living of Participants Who Were Unable to Complete the 6MWT (Nonambulatory Participants), as Measured by the Egen Klassifikation (EK) Scale at Week 60 | Baseline | 3.5 units on a scale | Standard Deviation 1.61 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Participant and Parent/Caregiver Reported Activities of Daily Living of Participants Who Were Unable to Complete the 6MWT (Nonambulatory Participants), as Measured by the Egen Klassifikation (EK) Scale at Week 60 | Change at Week 60 | 0.4 units on a scale | Standard Deviation 1.5 |
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 60
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 60.
Time frame: Baseline (Week 48 of Study 007), Week 60
Population: Evaluable population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, who had sufficient baseline and on-treatment data in Study 007e to assess the measure of interest. 'Number analyzed'=participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/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 60 | Baseline: Physical functioning score | 63.8145 units on a scale | Standard Deviation 24.46918 |
| High-Dose Ataluren/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 60 | Change at Week 60: Physical functioning score | -0.5982 units on a scale | Standard Deviation 14.91137 |
| High-Dose Ataluren/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 60 | Baseline: Emotional functioning score | 76.852 units on a scale | Standard Deviation 21.153 |
| High-Dose Ataluren/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 60 | Change at Week 60: Emotional functioning score | -1.675 units on a scale | Standard Deviation 13.6361 |
| High-Dose Ataluren/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 60 | Baseline: Social functioning score | 72.5000 units on a scale | Standard Deviation 21.60429 |
| High-Dose Ataluren/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 60 | Change at Week 60: Social functioning score | -2.2000 units on a scale | Standard Deviation 13.48317 |
| High-Dose Ataluren/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 60 | Baseline: School functioning score | 72.019 units on a scale | Standard Deviation 20.7756 |
| High-Dose Ataluren/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 60 | Change at Week 60: School functioning score | -1.064 units on a scale | Standard Deviation 16.5153 |
| Low-Dose Ataluren/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 60 | Change at Week 60: Social functioning score | 0.8511 units on a scale | Standard Deviation 17.36185 |
| Low-Dose Ataluren/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 60 | Baseline: Social functioning score | 68.6111 units on a scale | Standard Deviation 21.37748 |
| Low-Dose Ataluren/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 60 | Change at Week 60: Physical functioning score | -1.2538 units on a scale | Standard Deviation 14.60384 |
| Low-Dose Ataluren/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 60 | Change at Week 60: School functioning score | -1.630 units on a scale | Standard Deviation 17.7029 |
| Low-Dose Ataluren/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 60 | Baseline: School functioning score | 71.111 units on a scale | Standard Deviation 18.2918 |
| Low-Dose Ataluren/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 60 | Change at Week 60: Emotional functioning score | 2.128 units on a scale | Standard Deviation 14.9181 |
| Low-Dose Ataluren/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 60 | Baseline: Emotional functioning score | 73.241 units on a scale | Standard Deviation 20.1681 |
| Low-Dose Ataluren/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 60 | Baseline: Physical functioning score | 63.3019 units on a scale | Standard Deviation 22.72039 |
| Placebo/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 60 | Baseline: School functioning score | 69.063 units on a scale | Standard Deviation 20.3861 |
| Placebo/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 60 | Baseline: Emotional functioning score | 73.265 units on a scale | Standard Deviation 22.2568 |
| Placebo/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 60 | Change at Week 60: Emotional functioning score | -0.995 units on a scale | Standard Deviation 13.1621 |
| Placebo/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 60 | Baseline: Social functioning score | 71.3000 units on a scale | Standard Deviation 21.32858 |
| Placebo/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 60 | Change at Week 60: Social functioning score | 0.3500 units on a scale | Standard Deviation 15.15237 |
| Placebo/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 60 | Change at Week 60: School functioning score | 1.809 units on a scale | Standard Deviation 16.9214 |
| Placebo/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 60 | Baseline: Physical functioning score | 60.4865 units on a scale | Standard Deviation 22.33484 |
| Placebo/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 60 | Change at Week 60: Physical functioning score | 1.2755 units on a scale | Standard Deviation 19.01169 |
| Overall Participants: 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 60 | Baseline: Emotional functioning score | 74.490 units on a scale | Standard Deviation 21.1086 |
| Overall Participants: 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 60 | Change at Week 60: Emotional functioning score | -0.223 units on a scale | Standard Deviation 13.9106 |
| Overall Participants: 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 60 | Change at Week 60: Physical functioning score | -0.1804 units on a scale | Standard Deviation 16.2357 |
| Overall Participants: 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 60 | Baseline: Physical functioning score | 62.5995 units on a scale | Standard Deviation 23.11654 |
| Overall Participants: 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 60 | Baseline: Social functioning score | 70.7911 units on a scale | Standard Deviation 21.3667 |
| Overall Participants: 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 60 | Change at Week 60: School functioning score | -0.286 units on a scale | Standard Deviation 16.9931 |
| Overall Participants: 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 60 | Baseline: School functioning score | 70.779 units on a scale | Standard Deviation 19.7213 |
| Overall Participants: 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 60 | Change at Week 60: Social functioning score | -0.3571 units on a scale | Standard Deviation 15.32468 |
Secondary
Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60
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 60.
Time frame: Baseline (Week 48 of Study 007), Week 60
Population: Evaluable population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, who had sufficient baseline and on-treatment data in Study 007e to assess the measure of interest. 'Number analyzed'=participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Baseline | 76.7968 units on a scale | Standard Deviation 18.3131 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Change at Week 60 | -2.0484 units on a scale | Standard Deviation 9.77928 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Change at Week 60 | 0.3650 units on a scale | Standard Deviation 15.94374 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Baseline | 72.7833 units on a scale | Standard Deviation 20.95237 |
| Placebo/High-Dose Ataluren | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Change at Week 60 | -1.8049 units on a scale | Standard Deviation 11.12724 |
| Placebo/High-Dose Ataluren | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Baseline | 72.5947 units on a scale | Standard Deviation 17.32956 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Change at Week 60 | -1.2005 units on a scale | Standard Deviation 12.42615 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 | Baseline | 74.1111 units on a scale | Standard Deviation 18.92041 |
Secondary
Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60
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 SAM for at least 9 consecutive days. SAM was used to record number of strides/minute following each visit. A stride is leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again. Percentage of time during active periods spent at no activity (0 steps/min), low activity (≤15 steps/min), medium activity (16-30 steps/min), and high activity (\>30 steps/min) were computed for each participant. 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 of Study 007), Week 60
Population: Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at no activity | 52.818 percentage of time | Standard Deviation 14.4129 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at no activity | -0.051 percentage of time | Standard Deviation 8.1776 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at low activity | 30.677 percentage of time | Standard Deviation 7.8531 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at low activity | 1.270 percentage of time | Standard Deviation 5.8178 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at medium activity | 10.248 percentage of time | Standard Deviation 4.762 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at medium activity | -0.542 percentage of time | Standard Deviation 2.096 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at high activity | 6.404 percentage of time | Standard Deviation 4.5938 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at high activity | -0.643 percentage of time | Standard Deviation 2.2656 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at no activity | 0.830 percentage of time | Standard Deviation 11.2481 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at medium activity | 10.119 percentage of time | Standard Deviation 4.4344 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at high activity | 5.370 percentage of time | Standard Deviation 3.4243 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at medium activity | -1.356 percentage of time | Standard Deviation 3.783 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at high activity | -0.520 percentage of time | Standard Deviation 2.7196 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at low activity | 1.172 percentage of time | Standard Deviation 8.305 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at low activity | 31.170 percentage of time | Standard Deviation 7.2431 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at no activity | 53.372 percentage of time | Standard Deviation 12.2352 |
| Placebo/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at high activity | 6.673 percentage of time | Standard Deviation 4.5847 |
| Placebo/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at low activity | 32.393 percentage of time | Standard Deviation 7.2426 |
| Placebo/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at low activity | 0.252 percentage of time | Standard Deviation 5.5885 |
| Placebo/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at high activity | -1.506 percentage of time | Standard Deviation 2.9904 |
| Placebo/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at medium activity | 10.983 percentage of time | Standard Deviation 4.6049 |
| Placebo/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at medium activity | -0.965 percentage of time | Standard Deviation 3.3763 |
| Placebo/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at no activity | 50.006 percentage of time | Standard Deviation 12.5263 |
| Placebo/High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at no activity | 2.194 percentage of time | Standard Deviation 7.8652 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at high activity | -0.898 percentage of time | Standard Deviation 2.6913 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at low activity | 0.896 percentage of time | Standard Deviation 6.6058 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at no activity | 0.985 percentage of time | Standard Deviation 9.1467 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at no activity | 52.094 percentage of time | Standard Deviation 13.1188 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at high activity | 6.149 percentage of time | Standard Deviation 4.2476 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at medium activity | 10.442 percentage of time | Standard Deviation 4.5901 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Baseline: Time spent at low activity | 31.392 percentage of time | Standard Deviation 7.4462 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 | Change at Week 60: Time spent at medium activity | -0.944 percentage of time | Standard Deviation 3.1392 |
Secondary
Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 60
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 of Study 007), Week 60
Population: Evaluable population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, who had sufficient baseline and on-treatment data in Study 007e to assess the measure of interest. 'Number analyzed'=participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 60 | Baseline | 9163.1 units/liter (U/L) | Standard Deviation 5542.8 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 60 | Change at Week 60 | -455.1 units/liter (U/L) | Standard Deviation 4962 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 60 | Change at Week 60 | -520.5 units/liter (U/L) | Standard Deviation 6164.96 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 60 | Baseline | 10009.1 units/liter (U/L) | Standard Deviation 5828.26 |
| Placebo/High-Dose Ataluren | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 60 | Baseline | 9150.7 units/liter (U/L) | Standard Deviation 5657.67 |
| Placebo/High-Dose Ataluren | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 60 | Change at Week 60 | -334.3 units/liter (U/L) | Standard Deviation 4810.45 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 60 | Change at Week 60 | -435.1 units/liter (U/L) | Standard Deviation 5310.37 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 60 | Baseline | 9442.8 units/liter (U/L) | Standard Deviation 5656.99 |
Secondary
Change From Baseline in Time to Climb 4 Stairs at Week 60
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 of Study 007), Week 60
Population: Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Climb 4 Stairs at Week 60 | Baseline | 9.077 seconds | Standard Deviation 9.2543 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Climb 4 Stairs at Week 60 | Change at Week 60 | 0.831 seconds | Standard Deviation 2.4664 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Climb 4 Stairs at Week 60 | Change at Week 60 | 0.696 seconds | Standard Deviation 4.0707 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Climb 4 Stairs at Week 60 | Baseline | 6.738 seconds | Standard Deviation 6.4069 |
| Placebo/High-Dose Ataluren | Change From Baseline in Time to Climb 4 Stairs at Week 60 | Baseline | 8.071 seconds | Standard Deviation 9.2057 |
| Placebo/High-Dose Ataluren | Change From Baseline in Time to Climb 4 Stairs at Week 60 | Change at Week 60 | 0.194 seconds | Standard Deviation 2.5268 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Time to Climb 4 Stairs at Week 60 | Baseline | 7.984 seconds | Standard Deviation 8.4076 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Time to Climb 4 Stairs at Week 60 | Change at Week 60 | 0.574 seconds | Standard Deviation 3.0898 |
Secondary
Change From Baseline in Time to Descend 4 Stairs at Week 60
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 of Study 007), Week 60
Population: Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Descend 4 Stairs at Week 60 | Baseline | 7.685 seconds | Standard Deviation 8.9934 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Descend 4 Stairs at Week 60 | Change at Week 60 | 1.167 seconds | Standard Deviation 4.7624 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Descend 4 Stairs at Week 60 | Change at Week 60 | 0.626 seconds | Standard Deviation 5.2567 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Descend 4 Stairs at Week 60 | Baseline | 5.638 seconds | Standard Deviation 5.5635 |
| Placebo/High-Dose Ataluren | Change From Baseline in Time to Descend 4 Stairs at Week 60 | Baseline | 6.641 seconds | Standard Deviation 7.8591 |
| Placebo/High-Dose Ataluren | Change From Baseline in Time to Descend 4 Stairs at Week 60 | Change at Week 60 | -0.648 seconds | Standard Deviation 4.9202 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Time to Descend 4 Stairs at Week 60 | Baseline | 6.675 seconds | Standard Deviation 7.6319 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Time to Descend 4 Stairs at Week 60 | Change at Week 60 | 0.385 seconds | Standard Deviation 5.0045 |
Secondary
Change From Baseline in Time to Stand From Supine Position at Week 60
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 of Study 007), Week 60
Population: Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Stand From Supine Position at Week 60 | Baseline | 13.736 seconds | Standard Deviation 11.3353 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Stand From Supine Position at Week 60 | Change at Week 60 | 0.665 seconds | Standard Deviation 3.008 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Stand From Supine Position at Week 60 | Change at Week 60 | -0.187 seconds | Standard Deviation 4.6289 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Stand From Supine Position at Week 60 | Baseline | 11.796 seconds | Standard Deviation 10.3544 |
| Placebo/High-Dose Ataluren | Change From Baseline in Time to Stand From Supine Position at Week 60 | Baseline | 12.398 seconds | Standard Deviation 11.601 |
| Placebo/High-Dose Ataluren | Change From Baseline in Time to Stand From Supine Position at Week 60 | Change at Week 60 | 0.002 seconds | Standard Deviation 4.6322 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Time to Stand From Supine Position at Week 60 | Baseline | 12.666 seconds | Standard Deviation 11.0678 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Time to Stand From Supine Position at Week 60 | Change at Week 60 | 0.166 seconds | Standard Deviation 4.1373 |
Secondary
Change From Baseline in Time to Walk/Run 10 Meters at Week 60
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 of Study 007), Week 60
Population: Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Walk/Run 10 Meters at Week 60 | Baseline | 8.143 seconds | Standard Deviation 5.1475 |
| High-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Walk/Run 10 Meters at Week 60 | Change at Week 60 | 1.441 seconds | Standard Deviation 4.4822 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Walk/Run 10 Meters at Week 60 | Change at Week 60 | 0.547 seconds | Standard Deviation 2.2058 |
| Low-Dose Ataluren/High-Dose Ataluren | Change From Baseline in Time to Walk/Run 10 Meters at Week 60 | Baseline | 6.986 seconds | Standard Deviation 2.9995 |
| Placebo/High-Dose Ataluren | Change From Baseline in Time to Walk/Run 10 Meters at Week 60 | Baseline | 6.967 seconds | Standard Deviation 3.5789 |
| Placebo/High-Dose Ataluren | Change From Baseline in Time to Walk/Run 10 Meters at Week 60 | Change at Week 60 | 0.758 seconds | Standard Deviation 2.6862 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Time to Walk/Run 10 Meters at Week 60 | Baseline | 7.384 seconds | Standard Deviation 4.053 |
| Overall Participants: High-Dose Ataluren | Change From Baseline in Time to Walk/Run 10 Meters at Week 60 | Change at Week 60 | 0.922 seconds | Standard Deviation 3.2905 |
Secondary
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 (Week 48 of Study 007) to Week 96
Population: As-treated population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Study Drug Compliance | 0.00 percentage of drug |
| Low-Dose Ataluren/High-Dose Ataluren | Study Drug Compliance | 0.00 percentage of drug |
| Placebo/High-Dose Ataluren | Study Drug Compliance | 0.00 percentage of drug |
| Overall Participants: High-Dose Ataluren | Study Drug Compliance | 0.00 percentage of drug |
Secondary
Trough Ataluren Plasma Concentration
Plasma samples for the determination of ataluren concentrations were analyzed at the bioanalytical laboratory for ataluren parent drug using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC/MS-MS) method with a lower limit of quantitation (LLOQ) of 0.5 micrograms/millilitre (mcg/mL). Values below the LLOQ were set to 0.
Time frame: Pre-morning dose (0 hour) at Baseline (Week 48 of 007 study), Weeks 54, 60, 72, 84, and 96
Population: As-treated population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e. 'Number analyzed'=participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-Dose Ataluren/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 84 | 15.232 mcg/mL | Standard Deviation 8.8909 |
| High-Dose Ataluren/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 72 | 12.279 mcg/mL | Standard Deviation 10.5894 |
| High-Dose Ataluren/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 60 | 11.547 mcg/mL | Standard Deviation 9.6034 |
| High-Dose Ataluren/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 54 | 10.801 mcg/mL | Standard Deviation 8.4858 |
| High-Dose Ataluren/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 96 | 8.430 mcg/mL | — |
| High-Dose Ataluren/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 48 | 12.656 mcg/mL | Standard Deviation 10.8951 |
| Low-Dose Ataluren/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 84 | 14.773 mcg/mL | Standard Deviation 10.4404 |
| Low-Dose Ataluren/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 96 | 5.685 mcg/mL | Standard Deviation 2.7648 |
| Low-Dose Ataluren/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 54 | 13.941 mcg/mL | Standard Deviation 14.5222 |
| Low-Dose Ataluren/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 60 | 13.830 mcg/mL | Standard Deviation 11.9096 |
| Low-Dose Ataluren/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 48 | 4.541 mcg/mL | Standard Deviation 3.4381 |
| Low-Dose Ataluren/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 72 | 13.930 mcg/mL | Standard Deviation 10.6393 |
| Placebo/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 48 | 0.000 mcg/mL | Standard Deviation 0 |
| Placebo/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 84 | 11.082 mcg/mL | Standard Deviation 14.6331 |
| Placebo/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 72 | 10.948 mcg/mL | Standard Deviation 6.3465 |
| Placebo/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 60 | 13.302 mcg/mL | Standard Deviation 9.4765 |
| Placebo/High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 54 | 11.564 mcg/mL | Standard Deviation 9.3312 |
| Overall Participants: High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 72 | 12.424 mcg/mL | Standard Deviation 9.4948 |
| Overall Participants: High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 48 | 5.773 mcg/mL | Standard Deviation 8.4333 |
| Overall Participants: High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 54 | 12.097 mcg/mL | Standard Deviation 11.1172 |
| Overall Participants: High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 60 | 12.890 mcg/mL | Standard Deviation 10.3574 |
| Overall Participants: High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 84 | 13.901 mcg/mL | Standard Deviation 10.7415 |
| Overall Participants: High-Dose Ataluren | Trough Ataluren Plasma Concentration | Week 96 | 6.600 mcg/mL | Standard Deviation 2.5167 |