Duchenne Muscular Dystrophy
Conditions
Keywords
Duchenne muscular dystrophy, Nonsense mutation, Premature stop codon, DMD, PTC124, Ataluren
Brief summary
Duchenne muscular dystrophy (DMD) 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 in approximately 10-15% of boys with the disease. Ataluren is an orally-delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2a extension trial that will evaluate the long-term safety of ataluren in boys with nonsense mutation DMD, as determined by adverse events and laboratory abnormalities. The study will also assess changes in walking, muscle function, strength, and other important clinical and laboratory measures.
Detailed description
This Phase 2a, multicenter, open-label safety and efficacy study will be performed at 3 sites in the United States. The study will enroll up to 38 participants with nonsense mutation Duchenne muscular dystrophy who participated in a previous Phase 2a study of ataluren (Protocol Number PTC124-GD-004-DMD \[NCT00264888\]). Participants will receive study drug 3 times per day (at breakfast, lunch, and dinner) for approximately 96 weeks (approximately 2 years). Study assessments will be performed at clinic visits during screening, every 6 weeks for the first 24 weeks, and then every 12 weeks until the end of the study. Additional safety laboratory testing, which may be performed at the investigational site or at an accredited local laboratory or clinic, is required every 3 weeks for the first 24 weeks and then every 6 weeks from Week 24 to Week 48. Participants will have a biceps muscle biopsy before ataluren treatment and again after 24 weeks of ataluren treatment to evaluate changes in muscle dystrophin expression. An evaluation of the effects of ataluren on corticosteroid pharmacokinetics will be performed. Associated with this ataluren clinical trial is a substudy that will use magnetic resonance evaluations to assess changes in the composition of muscles of the legs.
Interventions
DRUGAtaluren
Ataluren will be provided as a vanilla-flavored powder to be mixed with milk. Dosing based on participant body weight
Sponsors
Genzyme, a Sanofi Company
PTC Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
* Completion of ataluren treatment in the previous Phase 2a study (Protocol PTC124-GD-004-DMD). * Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if \<18 years of age). * Confirmed screening laboratory values within the central laboratory ranges. * In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren 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
* Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment. * Treatment with warfarin within 1 month prior to start of study treatment. * 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 \[colloidal silica\], and magnesium stearate). * Exposure to another investigational drug within 2 months prior to start of study treatment. * History of major surgical procedure within 1 month prior to start of study treatment. * Ongoing immunosuppressive therapy (other than corticosteroids). * Ongoing participation in any other clinical trial (except for sub-studies specifically approved by PTC Therapeutics). * Clinically significant symptoms and signs of congestive heart failure (CHF) (American College of Cardiology/American Heart Association Stage C or Stage D). * Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram findings, or laboratory abnormality that, in the Investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Baseline up to Week 89 | TEAE: any untoward medical occurrence or undesirable event(s) that begins or worsens following administration of the study drug, whether or not considered related to the treatment by the Investigator. Severity of an adverse event (AE) was classified as: mild (does not interfere with usual function), moderate (interferes with usual function; may require medical intervention), severe (interferes significantly with usual function; likely require medical intervention), life-threatening, and fatal. 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. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests | Baseline, Week 48 and Week 60 | Timed function tests included time to stand from supine position (rise to standing), time to run/walk 10 meters (m), and time to ascend/descend 4 stairs. Timed function tests were assessed in ambulatory participants. A decrease from baseline reflects faster completion of the functional task and, thus, better muscle function. If the time taken to perform a test exceeded 30 seconds or if a participant could not perform the test due to disease progression (PD), a value of 30 seconds was used. Test results were set to missing in the analysis for participants who could not perform the tests for reasons other than PD (for example, bone fracture). |
| Change From Baseline in Standing From Supine Position as Assessed by Method Scores During Timed Function Tests | Baseline, Week 48 and Week 60 | Timed test evaluations included scoring of method that ambulatory participants used to complete test. Scale for method used for standing from supine position: 1) Unable to stand from supine, even with use of a chair. 2) Assisted Gowers, requires furniture to rise from supine to full upright posture. 3) Full Gowers, rolls over, stands with both hands climbing up legs to above knees to achieve full upright posture. 4) Half Gowers, rolls over, stands up with 1 hand support on lower legs. 5) Rolls to side and/or stands with 1 or both hands on floor to start to rise but does not touch legs. 6) Stands without rolling over or using hands. Increases from baseline are indicative of improving ability to perform functional task. If a participant could not perform a timed function test because of PD, a method value of 1 was assigned in analysis. Test results set to missing in analysis for participants who could not perform tests for reasons other than PD (for example, bone fracture). |
| Change From Baseline in Run/Walk 10-Meters as Assessed by Method Scores During Timed Function Tests | Baseline, Week 48 and Week 60 | Timed test evaluations included scoring of method that ambulatory participants used to complete test. Scale for method used to run/walk 10-meters: 1) Unable to walk independently. 2) Unable to walk independently but can walk with knee-ankle-foot orthoses (KAFOs) or with support from a person 3) Highly adapted, wide-based lordotic gait, cannot increase walking speed. 4) Moderately adapted gait, can pick up speed but cannot run. 5) Able to pick up speed but runs with a double stance phase (that is, cannot achieve both feet off the ground). 6) Runs and gets both feet off the ground (with no double-stance phase). At the visit, if a participant could not perform a timed function test because of PD, a method value of 1 was assigned in analysis. Test results set to missing in analysis for participants who could not perform tests for reasons other than PD (for example, bone fracture). |
| Change From Baseline in Ascending 4 Stairs as Assessed by Method Scores During Timed Function Tests | Baseline, Week 48 and Week 60 | Timed test evaluations included scoring of method that ambulatory participants used to complete test. Scale for method used to ascend 4 stairs: 1) Unable to climb 4 standard stairs. 2) Climbs 4 standard stairs marking time (climbs 1 foot at a time, with both feet on a step before moving to next step), using both arms on 1 or both handrails. 3) Climbs 4 standard stairs marking time using 1 arm on 1 handrail. 4) Climbs 4 standard stairs marking time not needing handrail. 5) Climbs 4 standard stairs alternating feet, needs handrail for support. 6) Climbs 4 standard stairs alternating feet, not needing handrail support. At the visit, if a participant could not perform a timed function test because of PD, a method value of 1 was assigned in analysis. Test results set to missing in analysis for participants who could not perform tests for reasons other than PD (for example, bone fracture). |
| Change From Baseline in Descending 4 Stairs as Assessed by Method Scores During Timed Function Tests | Baseline, Week 48 and Week 60 | Timed test evaluations included scoring of method that ambulatory participants used to complete test. Scale for method used to descend 4 stairs: 1) Unable to descend 4 standard stairs. 2) Descends 4 standard stairs marking time (climbs 1 foot at a time, with both feet on a step before moving to next step), using both arms on 1 or both handrails. 3) Descends 4 standard stairs marking time, using 1 arm on 1 handrail. 4) Descends 4 standard stairs marking time, not needing handrail. 5) Descends 4 standard stairs alternating feet in both directions, needs handrail for support. 6) Descends 4 standard stairs alternating feet, not needing handrail support. At the visit, if a participant could not perform a timed function test because of PD, a method value of 1 was assigned in analysis. Test results set to missing in analysis for participants who could not perform tests for reasons other than PD (for example, bone fracture). |
| Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | Baseline, Week (Wk) 48 and Wk 60 | Upper extremity myometry was performed using a hand-held dynamometer following standardized procedures. With this system, evaluators judged the strength of each muscle using an 11-point descriptive scoring system. From the individual muscle-group scores, a total composite score was derived. Bilateral assessments were done, and 3 measurements were recorded from each muscle group on each side, when possible. The best of the 3 replicates was used in the analysis. An increase from Baseline is reflective of increased muscle strength, whereas a decrease from Baseline is reflective of decreased muscle strength. Participants who became unable to perform a myometry test because of disease progression were assigned a value of 0 for each visit at which the participant was no longer able to perform the test. Test results were set to missing in the analysis for participants who could not perform the tests for reasons other than disease progression (for example, bone fracture). |
| Change in Resting, Active, and Recovery Heart Rate as Assessed by Heart Rate Monitoring With the Polar RS400 | Baseline, Week 48 and Week 60 | 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 rate values were collected before, during, and after the 6MWT. The participant rested for 5 minutes in a sitting position before the 6MWT, and the mean heart rate for the last minute of this rest period was obtained 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 obtained and documented as the recovery heart rate. |
| Change From Baseline in Verbal Memory and Attention as Assessed by the Digit Span Task | Baseline, Week 48 and Week 60 | The digit span task is a 2-part (forward and backward) test in which a series of digits (3 to 9) were presented to participant in an auditory format only. For forward condition, the participant was to repeat digits back in the order they were presented. For backward condition, the participant was to reverse the order of presentation. Maximum score for each part (digit forward and digit backward) of task is 14; participants received a score of 2 points if they passed both trials, score of 1 point if they passed only 1 trial, and score of 0 points if they failed both trials. A raw score of total number of correct forward and backward responses was age-normalized by subtracting corresponding mean and dividing by corresponding standard deviation of a reference population for that age. For each forward and backward result, the resulting Z score was transformed into percentile rank of normal distribution. Change from Baseline in number of digits recalled forward and backward is reported. |
| Change From Baseline in 6-Minute Walk Distance (6MWD) as Measured by the 6-minute Walk Test (6MWT) | Baseline, Week 48 and Week 60 | The 6MWD was assessed in participants who were ambulatory using standardized procedures. Participants were not permitted to use assistive devices during the 6MWD test. Only the results of the participant's best valid test at each visit were included in the analysis. The mean change from baseline in the distance the participant walked is reported. |
| Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Baseline, Week 48 and Week 60 | The PedsQL Generic Core Scales comprises 23 questions, which are grouped into 4 scales (physical functioning, emotional functioning, social functioning, and school functioning); the fatigue-specific module included an additional 18 questions. The appropriate age-specific version was completed. On PedsQL Generic Core Scales, items were reversed scored and linearly transformed to a 0 to 100 scale so that higher scores indicate a better HRQL (0=100, 1=75, 2=50, 3=25, and 4=0). Mean is the sum of the items over the number of items that were answered (which accounts for missing data) to create scale scores. If \>50% of the items in a scale were missing, the scale score was not computed. Mean Fatigue Scale Score is the sum of the items over the number of items that were answered in the Emotional, Social, and School Functioning Scales. Mean Total Scale Score is the sum of all of the items over the number of items that were answered on all scales. |
| Change From Baseline in Serum Creatine Kinase (CK) Levels | Baseline, Week 48 and Week 60 | Serum CK concentrations (as measured by the central laboratory) were quantified from the blood samples that were collected as part of the safety laboratory evaluations. The normal range for CK is 18 to 363 units/liter (U/L). |
| Change From Baseline in Dystrophin Expression on Biceps Muscle Biopsy as Measured by Immunofluorescence Staining of the Sarcolemmal Membrane With an Antibody to the C-Terminal Portion of the Dystrophin Protein | Baseline, Week 24 | The biceps muscle was biopsied from 1 arm for confirmation of the absence or low levels of dystrophin prior to treatment initiation and from the other arm to assess for production of dystrophin post-treatment. Muscle tissue sections were processed and immunostained to detect muscle membrane-localized dystrophin. An increase in value indicates dystrophin production. |
| Study Drug Compliance | Baseline up to Week 89 | Study drug compliance was assessed by the participant daily diary and quantification of used and unused study drug. Compliance was assessed in terms of the amount of drug actually taken relative to the amount that was prescribed. Physician-prescribed dose reductions and interruptions were factored into the calculations. Not recorded applies only to the days on which all dosing information was missing or for missing days. Invalid entries in the participant daily diary were assigned values of 0.0 for percentage of doses taken and 99.0 for percentage of doses not recorded. |
| Pharmacokinetics: Ataluren Plasma Exposure in All Participants | 0 (pre-dose), 0.5, 1, 2, 3, and 4 hours post-morning dose and 0 (pre-dose) and 2 hours post-midday dose on Day 2 of Week 1 and Day 2 of Week 6 | Blood for ataluren concentrations over a 24-hour period was to be collected on Day 2 of Week 1 and Day 2 of Week 6. Analysis of the blood samples was to be conducted 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/milliliters (μg/mL). Plasma concentrations below qualification (BQ) is treated as 0 in the summary calculation. |
| Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | 0 (pre-dose), 0.5, 1, 2, 3, and 4 hours post-morning dose and 0 (pre-dose) and 2 hours post-midday dose on Day 2 of Week 1 and Day 2 of Week 6 | Blood for ataluren concentrations were collected on Day 2 of Week 1 and Day 2 of Week 6. Analysis of the blood samples was to be conducted using a validated HPLC-MS/MS method with a LLOQ of 0.5 μg/mL. Plasma concentrations BQ is treated as 0 in the summary calculation. |
| Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 0 (pre-dose), 0.5, 1, 2, 3, and 4 hours post-morning dose and 0 (pre-dose) and 2 hours post-midday dose on Day 2 of Week 1 and Day 2 of Week 6 | Blood for prednisone and deflazacort concentrations were collected on Day 2 of Week 1 and Day 2 of Week 6. Plasma samples for the determination of prednisone concentrations were analyzed using a validated HPLC/MS/MS method, with LLOQs of 1.00 nanograms/milliliters (ng/mL). Prednisone concentrations \<1.01 are treated as 1.01 in the summary calculation. Plasma samples for the determination of 21-desacetyl deflazacort concentrations were analyzed using a validated HPLC/MS/MS method with an LLOQ of 1.0 ng/mL. Deflazacort concentrations BQ are treated as 0 in the summary calculation. |
| Change in Muscle Composition as Assessed by Limb Magnetic Resonance (MR) Testing | Baseline, Week 48, Week 60 | This Outcome Measure is an exploratory study objective and data were not collected or analyzed for this extension study. |
| Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Baseline, Week 48 and Week 60 | The PedsQL Generic Core Scales comprises 23 questions, which are grouped into 4 scales (physical functioning, emotional functioning, social functioning, and school functioning); the fatigue-specific module included an additional 18 questions. The appropriate age-specific version was completed. On PedsQL Generic Core Scales, items were reversed scored and linearly transformed to a 0 to 100 scale so that higher scores indicate a better HRQL (0=100, 1=75, 2=50, 3=25, and 4=0). Mean is the sum of the items over the number of items that were answered (which accounts for missing data) to create scale scores. If \>50% of the items in a scale were missing, the scale score was not computed. Mean Total Scale Score is the sum of all of the items over the number of items that were answered on all scales. |
Countries
United States
Participant flow
Recruitment details
This extension study was initiated approximately 2 years after the completion of Study PTC124-GD-004-DMD (Study 004 \[NCT00264888\]).
Pre-assignment details
Of the 36 participants, 11 received 20-, 20-, and 40-milligrams/kilograms (mg/kg); 20 received 10-, 10-, and 20-mg/kg; and 5 received 4-, 4-, and 8-mg/kg ataluren dose level in Study 004. The 31 participants receiving corticosteroid treatment at study entry could continue corticosteroid treatment during the study as long as regimen remained stable.
Participants by arm
| Arm | Count |
|---|---|
| Ataluren Participants received ataluren 3 times per day with meals at doses of 20 mg/kg (breakfast), 20 mg/kg (lunch), and 40 mg/kg (dinner) for up to 89 weeks. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Sponsor terminated study early | 36 |
Baseline characteristics
| Characteristic | Ataluren |
|---|---|
| Age, Continuous | 11.6 years STANDARD_DEVIATION 2.61 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 36 |
| serious Total, serious adverse events | 6 / 36 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAE: any untoward medical occurrence or undesirable event(s) that begins or worsens following administration of the study drug, whether or not considered related to the treatment by the Investigator. Severity of an adverse event (AE) was classified as: mild (does not interfere with usual function), moderate (interferes with usual function; may require medical intervention), severe (interferes significantly with usual function; likely require medical intervention), life-threatening, and fatal. 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. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline up to Week 89
Population: All enrolled participants who received at least 1 dose of study drug (As-Treated Population).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ataluren | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | At least 1 TEAE | 36 Participants |
| Ataluren | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Mild TEAE | 9 Participants |
| Ataluren | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Moderate TEAE | 16 Participants |
| Ataluren | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Severe TEAE | 10 Participants |
| Ataluren | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Life-Threatening TEAE | 1 Participants |
| Ataluren | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Fatal TEAE | 0 Participants |
| Ataluren | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Related TEAE | 28 Participants |
| Ataluren | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Serious TEAE | 6 Participants |
Secondary
Change From Baseline in 6-Minute Walk Distance (6MWD) as Measured by the 6-minute Walk Test (6MWT)
The 6MWD was assessed in participants who were ambulatory using standardized procedures. Participants were not permitted to use assistive devices during the 6MWD test. Only the results of the participant's best valid test at each visit were included in the analysis. The mean change from baseline in the distance the participant walked is reported.
Time frame: Baseline, Week 48 and Week 60
Population: All enrolled participants who received at least 1 dose of study drug, were ambulatory, and had evaluable 6MWT data. Participants who were ambulatory were able to walk ≥75 meters unassisted at screening.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Change From Baseline in 6-Minute Walk Distance (6MWD) as Measured by the 6-minute Walk Test (6MWT) | Change from Baseline at Week 48 | -80.4 meters | Standard Deviation 59.5 |
| Ataluren | Change From Baseline in 6-Minute Walk Distance (6MWD) as Measured by the 6-minute Walk Test (6MWT) | Baseline | 367.8 meters | Standard Deviation 107.3 |
| Ataluren | Change From Baseline in 6-Minute Walk Distance (6MWD) as Measured by the 6-minute Walk Test (6MWT) | Change from Baseline at Week 60 | -101.5 meters | Standard Deviation 64.4 |
Secondary
Change From Baseline in Ascending 4 Stairs as Assessed by Method Scores During Timed Function Tests
Timed test evaluations included scoring of method that ambulatory participants used to complete test. Scale for method used to ascend 4 stairs: 1) Unable to climb 4 standard stairs. 2) Climbs 4 standard stairs marking time (climbs 1 foot at a time, with both feet on a step before moving to next step), using both arms on 1 or both handrails. 3) Climbs 4 standard stairs marking time using 1 arm on 1 handrail. 4) Climbs 4 standard stairs marking time not needing handrail. 5) Climbs 4 standard stairs alternating feet, needs handrail for support. 6) Climbs 4 standard stairs alternating feet, not needing handrail support. At the visit, if a participant could not perform a timed function test because of PD, a method value of 1 was assigned in analysis. Test results set to missing in analysis for participants who could not perform tests for reasons other than PD (for example, bone fracture).
Time frame: Baseline, Week 48 and Week 60
Population: All enrolled participants who received at least 1 dose of study drug, were ambulatory, and had evaluable method data for ascending 4 stairs. Participants who were ambulatory were able to walk ≥75 meters unassisted at screening.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Change From Baseline in Ascending 4 Stairs as Assessed by Method Scores During Timed Function Tests | Baseline | 3.58 scores on a scale | Standard Deviation 1.717 |
| Ataluren | Change From Baseline in Ascending 4 Stairs as Assessed by Method Scores During Timed Function Tests | Change from Baseline at Week 48 | -0.46 scores on a scale | Standard Deviation 1.141 |
| Ataluren | Change From Baseline in Ascending 4 Stairs as Assessed by Method Scores During Timed Function Tests | Change from Baseline at Week 60 | -0.48 scores on a scale | Standard Deviation 1.365 |
Secondary
Change From Baseline in Descending 4 Stairs as Assessed by Method Scores During Timed Function Tests
Timed test evaluations included scoring of method that ambulatory participants used to complete test. Scale for method used to descend 4 stairs: 1) Unable to descend 4 standard stairs. 2) Descends 4 standard stairs marking time (climbs 1 foot at a time, with both feet on a step before moving to next step), using both arms on 1 or both handrails. 3) Descends 4 standard stairs marking time, using 1 arm on 1 handrail. 4) Descends 4 standard stairs marking time, not needing handrail. 5) Descends 4 standard stairs alternating feet in both directions, needs handrail for support. 6) Descends 4 standard stairs alternating feet, not needing handrail support. At the visit, if a participant could not perform a timed function test because of PD, a method value of 1 was assigned in analysis. Test results set to missing in analysis for participants who could not perform tests for reasons other than PD (for example, bone fracture).
Time frame: Baseline, Week 48 and Week 60
Population: All enrolled participants who received at least 1 dose of study drug, were ambulatory, and had evaluable method data for descending 4 stairs. Participants who were ambulatory were able to walk ≥75 meters unassisted at screening.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Change From Baseline in Descending 4 Stairs as Assessed by Method Scores During Timed Function Tests | Baseline | 3.63 scores on a scale | Standard Deviation 1.74 |
| Ataluren | Change From Baseline in Descending 4 Stairs as Assessed by Method Scores During Timed Function Tests | Change from Baseline at Week 48 | -0.04 scores on a scale | Standard Deviation 1.16 |
| Ataluren | Change From Baseline in Descending 4 Stairs as Assessed by Method Scores During Timed Function Tests | Change from Baseline at Week 60 | -0.10 scores on a scale | Standard Deviation 0.889 |
Secondary
Change From Baseline in Dystrophin Expression on Biceps Muscle Biopsy as Measured by Immunofluorescence Staining of the Sarcolemmal Membrane With an Antibody to the C-Terminal Portion of the Dystrophin Protein
The biceps muscle was biopsied from 1 arm for confirmation of the absence or low levels of dystrophin prior to treatment initiation and from the other arm to assess for production of dystrophin post-treatment. Muscle tissue sections were processed and immunostained to detect muscle membrane-localized dystrophin. An increase in value indicates dystrophin production.
Time frame: Baseline, Week 24
Population: All enrolled participants who received at least 1 dose of study drug (As-Treated Population) and had evaluable dystrophin expression data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Change From Baseline in Dystrophin Expression on Biceps Muscle Biopsy as Measured by Immunofluorescence Staining of the Sarcolemmal Membrane With an Antibody to the C-Terminal Portion of the Dystrophin Protein | Baseline | 16.828 dystrophin positive fibers | Standard Deviation 8.4285 |
| Ataluren | Change From Baseline in Dystrophin Expression on Biceps Muscle Biopsy as Measured by Immunofluorescence Staining of the Sarcolemmal Membrane With an Antibody to the C-Terminal Portion of the Dystrophin Protein | Change from Baseline | -1.880 dystrophin positive fibers | Standard Deviation 5.1337 |
Secondary
Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry
Upper extremity myometry was performed using a hand-held dynamometer following standardized procedures. With this system, evaluators judged the strength of each muscle using an 11-point descriptive scoring system. From the individual muscle-group scores, a total composite score was derived. Bilateral assessments were done, and 3 measurements were recorded from each muscle group on each side, when possible. The best of the 3 replicates was used in the analysis. An increase from Baseline is reflective of increased muscle strength, whereas a decrease from Baseline is reflective of decreased muscle strength. Participants who became unable to perform a myometry test because of disease progression were assigned a value of 0 for each visit at which the participant was no longer able to perform the test. Test results were set to missing in the analysis for participants who could not perform the tests for reasons other than disease progression (for example, bone fracture).
Time frame: Baseline, Week (Wk) 48 and Wk 60
Population: All enrolled participants who received at least 1 dose of study drug and had Baseline and on-treatment data (Evaluable Population) with evaluable myometry data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | Left (L) Knee Flexion, Baseline | 9.48 pounds | Standard Deviation 4.395 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Knee Flexion, Change from Baseline at Wk 48 | 1.23 pounds | Standard Deviation 2.715 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Knee Flexion, Change from Baseline at Wk 60 | 0.64 pounds | Standard Deviation 3.079 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | Right (R) Knee Flexion, Baseline | 10.15 pounds | Standard Deviation 5.439 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Knee Flexion, Change from Baseline at Wk 48 | 0.81 pounds | Standard Deviation 2.254 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Knee Flexion, Change from Baseline at Wk 60 | -0.05 pounds | Standard Deviation 2.24 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Knee Extension, Baseline | 8.63 pounds | Standard Deviation 5.124 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Knee Extension, Change from Baseline at Wk 48 | -1.07 pounds | Standard Deviation 1.842 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Knee Extension, Change from Baseline at Wk 60 | -1.00 pounds | Standard Deviation 1.567 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Knee Extension, Baseline | 9.10 pounds | Standard Deviation 6.109 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Knee Extension, Change from Baseline at Wk 48 | -1.33 pounds | Standard Deviation 2.021 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Knee Extension, Change from Baseline at Wk 60 | -1.65 pounds | Standard Deviation 2.204 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Elbow Flexion, Baseline | 5.70 pounds | Standard Deviation 3.611 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Elbow Flexion, Change from Baseline at Wk 48 | -0.15 pounds | Standard Deviation 0.998 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Elbow Flexion, Change from Baseline at Wk 60 | -0.51 pounds | Standard Deviation 1.121 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Elbow Flexion, Baseline | 5.85 pounds | Standard Deviation 3.758 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Elbow Flexion, Change from Baseline at Wk 48 | -0.28 pounds | Standard Deviation 1.05 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Elbow Flexion, Change from Baseline at Wk 60 | -0.55 pounds | Standard Deviation 1.061 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Elbow Extension, Baseline | 4.55 pounds | Standard Deviation 2.322 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Elbow Extension, Change from Baseline at Wk 48 | -0.10 pounds | Standard Deviation 0.993 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Elbow Extension, Change from Baseline at Wk 60 | -0.32 pounds | Standard Deviation 0.818 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Elbow Extension, Baseline | 4.89 pounds | Standard Deviation 2.68 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Elbow Extension, Change from Baseline at Wk 48 | -0.10 pounds | Standard Deviation 1.6 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Elbow Extension, Change from Baseline at Wk 60 | -0.60 pounds | Standard Deviation 1.352 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Shoulder Abduction, Baseline | 4.29 pounds | Standard Deviation 2.783 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Shoulder Abduction Change from Baseline at Wk 48 | -0.90 pounds | Standard Deviation 0.906 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Shoulder Abduction Change from Baseline at Wk 60 | -1.10 pounds | Standard Deviation 1.632 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Shoulder Abduction, Baseline | 4.39 pounds | Standard Deviation 2.666 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Shoulder Abduction Change from Baseline at Wk 48 | -1.02 pounds | Standard Deviation 1.369 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Shoulder Abduction Change from Baseline at Wk 60 | -1.23 pounds | Standard Deviation 1.888 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Hand Grip, Baseline | 15.19 pounds | Standard Deviation 5.881 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Hand Grip, Change from Baseline at Wk 48 | 0.30 pounds | Standard Deviation 3.353 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | L Hand Grip, Change from Baseline at Wk 60 | 1.04 pounds | Standard Deviation 4.811 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Hand Grip, Baseline | 17.17 pounds | Standard Deviation 7.266 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Hand Grip, Change from Baseline at Wk 48 | -0.79 pounds | Standard Deviation 3.628 |
| Ataluren | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry | R Hand Grip, Change from Baseline at Wk 60 | -0.61 pounds | Standard Deviation 3.01 |
Secondary
Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory
The PedsQL Generic Core Scales comprises 23 questions, which are grouped into 4 scales (physical functioning, emotional functioning, social functioning, and school functioning); the fatigue-specific module included an additional 18 questions. The appropriate age-specific version was completed. On PedsQL Generic Core Scales, items were reversed scored and linearly transformed to a 0 to 100 scale so that higher scores indicate a better HRQL (0=100, 1=75, 2=50, 3=25, and 4=0). Mean is the sum of the items over the number of items that were answered (which accounts for missing data) to create scale scores. If \>50% of the items in a scale were missing, the scale score was not computed. Mean Fatigue Scale Score is the sum of the items over the number of items that were answered in the Emotional, Social, and School Functioning Scales. Mean Total Scale Score is the sum of all of the items over the number of items that were answered on all scales.
Time frame: Baseline, Week 48 and Week 60
Population: All enrolled participants who received at least 1 dose of study drug and had Baseline and on-treatment data (Evaluable Population) with evaluable parent- or caregiver-reported PedsQL data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Physical Functioning, Baseline | 48.07 scores on a scale | Standard Deviation 21.111 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Physical Functioning Change from Baseline at Wk 48 | 2.31 scores on a scale | Standard Deviation 20.284 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Physical Functioning Change from Baseline at Wk 60 | 1.85 scores on a scale | Standard Deviation 19.366 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Emotional Functioning, Baseline | 69.45 scores on a scale | Standard Deviation 17.465 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Emotional Function, Change from Baseline at Wk 48 | 5.27 scores on a scale | Standard Deviation 19.595 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Emotional Function, Change from Baseline at Wk 60 | 3.29 scores on a scale | Standard Deviation 20.021 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Social Functioning, Baseline | 57.95 scores on a scale | Standard Deviation 19.397 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Social Functioning, Change from Baseline at Wk 48 | 9.38 scores on a scale | Standard Deviation 16.956 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Social Functioning, Change from Baseline at Wk 60 | 6.16 scores on a scale | Standard Deviation 17.599 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | School Functioning, Baseline | 67.61 scores on a scale | Standard Deviation 14.944 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | School Functioning, Change from Baseline at Wk 48 | 5.66 scores on a scale | Standard Deviation 15.824 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | School Functioning, Change from Baseline at Wk 60 | -0.37 scores on a scale | Standard Deviation 10.651 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Fatigue Scale Score, Baseline | 72.25 scores on a scale | Standard Deviation 13.777 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Fatigue Scale Score, Change from Baseline at Wk 48 | 0.77 scores on a scale | Standard Deviation 9.703 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Fatigue Scale Score, Change from Baseline at Wk 60 | -0.40 scores on a scale | Standard Deviation 9.269 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Total Score, Baseline | 59.08 scores on a scale | Standard Deviation 13.348 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Total Score, Change from Baseline at Wk 48 | 5.24 scores on a scale | Standard Deviation 11.409 |
| Ataluren | Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory | Total Score, Change from Baseline at Wk 60 | 2.68 scores on a scale | Standard Deviation 12.261 |
Secondary
Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory
The PedsQL Generic Core Scales comprises 23 questions, which are grouped into 4 scales (physical functioning, emotional functioning, social functioning, and school functioning); the fatigue-specific module included an additional 18 questions. The appropriate age-specific version was completed. On PedsQL Generic Core Scales, items were reversed scored and linearly transformed to a 0 to 100 scale so that higher scores indicate a better HRQL (0=100, 1=75, 2=50, 3=25, and 4=0). Mean is the sum of the items over the number of items that were answered (which accounts for missing data) to create scale scores. If \>50% of the items in a scale were missing, the scale score was not computed. Mean Total Scale Score is the sum of all of the items over the number of items that were answered on all scales.
Time frame: Baseline, Week 48 and Week 60
Population: All enrolled participants who received at least 1 dose of study drug and had Baseline and on-treatment data (Evaluable Population) with evaluable participant-reported PedsQL data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Physical Functioning, Baseline | 45.13 scores on a scale | Standard Deviation 21.114 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Physical Functioning Change from Baseline at Wk 48 | 3.16 scores on a scale | Standard Deviation 20.18 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Physical Functioning Change from Baseline at Wk 60 | 6.25 scores on a scale | Standard Deviation 23.545 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Emotional Functioning, Baseline | 65.29 scores on a scale | Standard Deviation 16.141 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Emotional Function, Change from Baseline at Wk 48 | 8.24 scores on a scale | Standard Deviation 18.294 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Emotional Function, Change from Baseline at Wk 60 | 12.22 scores on a scale | Standard Deviation 17.614 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Social Functioning, Baseline | 61.80 scores on a scale | Standard Deviation 16.914 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Social Functioning, Change from Baseline at Wk 48 | 4.82 scores on a scale | Standard Deviation 19.463 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Social Functioning, Change from Baseline at Wk 60 | 3.75 scores on a scale | Standard Deviation 15.861 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | School Functioning, Baseline | 70.29 scores on a scale | Standard Deviation 16.466 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | School Functioning, Change from Baseline at Wk 48 | 1.76 scores on a scale | Standard Deviation 17.917 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | School Functioning, Change from Baseline at Wk 60 | 3.29 scores on a scale | Standard Deviation 16.273 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Fatigue Scale Score, Baseline | 74.28 scores on a scale | Standard Deviation 14.917 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Fatigue Scale Score, Change from Baseline at Wk 48 | 5.08 scores on a scale | Standard Deviation 12.661 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Fatigue Scale Score, Change from Baseline at Wk 60 | 4.39 scores on a scale | Standard Deviation 11.777 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Total Score, Baseline | 58.59 scores on a scale | Standard Deviation 12.793 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Total Score, Change from Baseline at Wk 48 | 4.28 scores on a scale | Standard Deviation 13.406 |
| Ataluren | Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory | Total Score, Change from Baseline at Wk 60 | 6.42 scores on a scale | Standard Deviation 10.887 |
Secondary
Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests
Timed function tests included time to stand from supine position (rise to standing), time to run/walk 10 meters (m), and time to ascend/descend 4 stairs. Timed function tests were assessed in ambulatory participants. A decrease from baseline reflects faster completion of the functional task and, thus, better muscle function. If the time taken to perform a test exceeded 30 seconds or if a participant could not perform the test due to disease progression (PD), a value of 30 seconds was used. Test results were set to missing in the analysis for participants who could not perform the tests for reasons other than PD (for example, bone fracture).
Time frame: Baseline, Week 48 and Week 60
Population: All enrolled participants who received at least 1 dose of study drug, were ambulatory, and had evaluable data for the applicable timed function test. Participants who were ambulatory were able to walk ≥75 meters unassisted at screening.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests | Rise to Standing, Baseline | 13.57 seconds | Standard Deviation 11.111 |
| Ataluren | Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests | Rise to Standing, Change from Baseline at Week 48 | 6.49 seconds | Standard Deviation 8.059 |
| Ataluren | Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests | Rise to Standing, Change from Baseline at Week 60 | 5.77 seconds | Standard Deviation 7.79 |
| Ataluren | Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests | Walk/Run 10 m, Baseline | 7.62 seconds | Standard Deviation 3.641 |
| Ataluren | Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests | Walk/Run 10 m, Change from Baseline at Week 48 | 3.15 seconds | Standard Deviation 5.591 |
| Ataluren | Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests | Walk/Run 10 m, Change from Baseline at Week 60 | 3.20 seconds | Standard Deviation 5.93 |
| Ataluren | Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests | Ascend 4 Stairs, Baseline | 7.16 seconds | Standard Deviation 7.481 |
| Ataluren | Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests | Ascend 4 Stairs, Change from Baseline at Week 48 | 4.92 seconds | Standard Deviation 6.856 |
| Ataluren | Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests | Ascend 4 Stairs, Change from Baseline at Week 60 | 6.30 seconds | Standard Deviation 7.926 |
| Ataluren | Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests | Descend 4 Stairs, Baseline | 6.42 seconds | Standard Deviation 7.565 |
| Ataluren | Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests | Descend 4 Stairs, Change from Baseline at Week 48 | 5.25 seconds | Standard Deviation 8.839 |
| Ataluren | Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests | Descend 4 Stairs, Change from Baseline at Week 60 | 4.28 seconds | Standard Deviation 7.275 |
Secondary
Change From Baseline in Run/Walk 10-Meters as Assessed by Method Scores During Timed Function Tests
Timed test evaluations included scoring of method that ambulatory participants used to complete test. Scale for method used to run/walk 10-meters: 1) Unable to walk independently. 2) Unable to walk independently but can walk with knee-ankle-foot orthoses (KAFOs) or with support from a person 3) Highly adapted, wide-based lordotic gait, cannot increase walking speed. 4) Moderately adapted gait, can pick up speed but cannot run. 5) Able to pick up speed but runs with a double stance phase (that is, cannot achieve both feet off the ground). 6) Runs and gets both feet off the ground (with no double-stance phase). At the visit, if a participant could not perform a timed function test because of PD, a method value of 1 was assigned in analysis. Test results set to missing in analysis for participants who could not perform tests for reasons other than PD (for example, bone fracture).
Time frame: Baseline, Week 48 and Week 60
Population: All enrolled participants who received at least 1 dose of study drug, were ambulatory, and had evaluable method data for running/walking 10 meters. Participants who were ambulatory were able to walk ≥75 meters unassisted at screening.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Change From Baseline in Run/Walk 10-Meters as Assessed by Method Scores During Timed Function Tests | Baseline | 4.42 scores on a scale | Standard Deviation 0.974 |
| Ataluren | Change From Baseline in Run/Walk 10-Meters as Assessed by Method Scores During Timed Function Tests | Change from Baseline at Week 48 | -0.25 scores on a scale | Standard Deviation 1.073 |
| Ataluren | Change From Baseline in Run/Walk 10-Meters as Assessed by Method Scores During Timed Function Tests | Change from Baseline at Week 60 | -0.57 scores on a scale | Standard Deviation 1.207 |
Secondary
Change From Baseline in Serum Creatine Kinase (CK) Levels
Serum CK concentrations (as measured by the central laboratory) were quantified from the blood samples that were collected as part of the safety laboratory evaluations. The normal range for CK is 18 to 363 units/liter (U/L).
Time frame: Baseline, Week 48 and Week 60
Population: All enrolled participants who received at least 1 dose of study drug and had Baseline and on-treatment data (Evaluable Population) with evaluable CK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Change From Baseline in Serum Creatine Kinase (CK) Levels | Baseline | 5988.31 U/L | Standard Deviation 3967.714 |
| Ataluren | Change From Baseline in Serum Creatine Kinase (CK) Levels | Change from Baseline at Week 48 | 84.06 U/L | Standard Deviation 2641.422 |
| Ataluren | Change From Baseline in Serum Creatine Kinase (CK) Levels | Change from Baseline at Week 60 | -549.57 U/L | Standard Deviation 3261.151 |
Secondary
Change From Baseline in Standing From Supine Position as Assessed by Method Scores During Timed Function Tests
Timed test evaluations included scoring of method that ambulatory participants used to complete test. Scale for method used for standing from supine position: 1) Unable to stand from supine, even with use of a chair. 2) Assisted Gowers, requires furniture to rise from supine to full upright posture. 3) Full Gowers, rolls over, stands with both hands climbing up legs to above knees to achieve full upright posture. 4) Half Gowers, rolls over, stands up with 1 hand support on lower legs. 5) Rolls to side and/or stands with 1 or both hands on floor to start to rise but does not touch legs. 6) Stands without rolling over or using hands. Increases from baseline are indicative of improving ability to perform functional task. If a participant could not perform a timed function test because of PD, a method value of 1 was assigned in analysis. Test results set to missing in analysis for participants who could not perform tests for reasons other than PD (for example, bone fracture).
Time frame: Baseline, Week 48 and Week 60
Population: All enrolled participants who received at least 1 dose of study drug, were ambulatory, and had evaluable method data for standing from supine. Participants who were ambulatory were able to walk ≥75 meters unassisted at screening.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Change From Baseline in Standing From Supine Position as Assessed by Method Scores During Timed Function Tests | Baseline | 3.25 scores on a scale | Standard Deviation 1.26 |
| Ataluren | Change From Baseline in Standing From Supine Position as Assessed by Method Scores During Timed Function Tests | Change from Baseline at Week 48 | -0.58 scores on a scale | Standard Deviation 0.929 |
| Ataluren | Change From Baseline in Standing From Supine Position as Assessed by Method Scores During Timed Function Tests | Change from Baseline at Week 60 | -0.62 scores on a scale | Standard Deviation 0.921 |
Secondary
Change From Baseline in Verbal Memory and Attention as Assessed by the Digit Span Task
The digit span task is a 2-part (forward and backward) test in which a series of digits (3 to 9) were presented to participant in an auditory format only. For forward condition, the participant was to repeat digits back in the order they were presented. For backward condition, the participant was to reverse the order of presentation. Maximum score for each part (digit forward and digit backward) of task is 14; participants received a score of 2 points if they passed both trials, score of 1 point if they passed only 1 trial, and score of 0 points if they failed both trials. A raw score of total number of correct forward and backward responses was age-normalized by subtracting corresponding mean and dividing by corresponding standard deviation of a reference population for that age. For each forward and backward result, the resulting Z score was transformed into percentile rank of normal distribution. Change from Baseline in number of digits recalled forward and backward is reported.
Time frame: Baseline, Week 48 and Week 60
Population: All enrolled participants who received at least 1 dose of study drug and had Baseline and on-treatment data (Evaluable Population) with evaluable verbal memory and attention data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Change From Baseline in Verbal Memory and Attention as Assessed by the Digit Span Task | Recalled Forward, Baseline | 3.66 digits recalled | Standard Deviation 2.378 |
| Ataluren | Change From Baseline in Verbal Memory and Attention as Assessed by the Digit Span Task | Recalled Forward, Change from Baseline at Wk 48 | 0.14 digits recalled | Standard Deviation 1.353 |
| Ataluren | Change From Baseline in Verbal Memory and Attention as Assessed by the Digit Span Task | Recalled Forward, Change from Baseline at Wk 60 | 0.04 digits recalled | Standard Deviation 1.453 |
| Ataluren | Change From Baseline in Verbal Memory and Attention as Assessed by the Digit Span Task | Recalled Backward, Baseline | 3.15 digits recalled | Standard Deviation 2.524 |
| Ataluren | Change From Baseline in Verbal Memory and Attention as Assessed by the Digit Span Task | Recalled Backward, Change from Baseline at Wk 48 | 0.74 digits recalled | Standard Deviation 1.442 |
| Ataluren | Change From Baseline in Verbal Memory and Attention as Assessed by the Digit Span Task | Recalled Backward, Change from Baseline at Wk 60 | 0.74 digits recalled | Standard Deviation 1.442 |
Secondary
Change in Muscle Composition as Assessed by Limb Magnetic Resonance (MR) Testing
This Outcome Measure is an exploratory study objective and data were not collected or analyzed for this extension study.
Time frame: Baseline, Week 48, Week 60
Population: All enrolled participants who received at least 1 dose of study drug and had Baseline and on-treatment data (Evaluable Population) with evaluable muscle composition data. Muscle composition data were not collected or analyzed for this extension study.
Secondary
Change in Resting, Active, and Recovery Heart Rate as Assessed by Heart Rate Monitoring With the Polar RS400
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 rate values were collected before, during, and after the 6MWT. The participant rested for 5 minutes in a sitting position before the 6MWT, and the mean heart rate for the last minute of this rest period was obtained 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 obtained and documented as the recovery heart rate.
Time frame: Baseline, Week 48 and Week 60
Population: All enrolled participants who received at least 1 dose of study drug, were ambulatory, and had evaluable heart rate data. Participants who were ambulatory were able to walk ≥75 meters unassisted at screening.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Change in Resting, Active, and Recovery Heart Rate as Assessed by Heart Rate Monitoring With the Polar RS400 | Recovery Heart Rate, Baseline | 113.13 beeps per minute | Standard Deviation 12.664 |
| Ataluren | Change in Resting, Active, and Recovery Heart Rate as Assessed by Heart Rate Monitoring With the Polar RS400 | Resting Heart Rate, Baseline | 106.46 beeps per minute | Standard Deviation 11.163 |
| Ataluren | Change in Resting, Active, and Recovery Heart Rate as Assessed by Heart Rate Monitoring With the Polar RS400 | Resting Heart Rate, Change from Baseline at Wk 48 | 8.30 beeps per minute | Standard Deviation 12.382 |
| Ataluren | Change in Resting, Active, and Recovery Heart Rate as Assessed by Heart Rate Monitoring With the Polar RS400 | Resting Heart Rate, Change from Baseline at Wk 60 | 5.16 beeps per minute | Standard Deviation 11.197 |
| Ataluren | Change in Resting, Active, and Recovery Heart Rate as Assessed by Heart Rate Monitoring With the Polar RS400 | Active Heart Rate, Baseline | 152.17 beeps per minute | Standard Deviation 13.457 |
| Ataluren | Change in Resting, Active, and Recovery Heart Rate as Assessed by Heart Rate Monitoring With the Polar RS400 | Active Heart Rate, Change from Baseline at Wk 48 | 3.86 beeps per minute | Standard Deviation 12.365 |
| Ataluren | Change in Resting, Active, and Recovery Heart Rate as Assessed by Heart Rate Monitoring With the Polar RS400 | Active Heart Rate, Change from Baseline at Wk 60 | -2.84 beeps per minute | Standard Deviation 17.238 |
| Ataluren | Change in Resting, Active, and Recovery Heart Rate as Assessed by Heart Rate Monitoring With the Polar RS400 | Recovery Heart Rate, Change from Baseline at Wk 48 | 4.64 beeps per minute | Standard Deviation 9.079 |
| Ataluren | Change in Resting, Active, and Recovery Heart Rate as Assessed by Heart Rate Monitoring With the Polar RS400 | Recovery Heart Rate, Change from Baseline at Wk 60 | 1.68 beeps per minute | Standard Deviation 15.688 |
Secondary
Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort
Blood for prednisone and deflazacort concentrations were collected on Day 2 of Week 1 and Day 2 of Week 6. Plasma samples for the determination of prednisone concentrations were analyzed using a validated HPLC/MS/MS method, with LLOQs of 1.00 nanograms/milliliters (ng/mL). Prednisone concentrations \<1.01 are treated as 1.01 in the summary calculation. Plasma samples for the determination of 21-desacetyl deflazacort concentrations were analyzed using a validated HPLC/MS/MS method with an LLOQ of 1.0 ng/mL. Deflazacort concentrations BQ are treated as 0 in the summary calculation.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, and 4 hours post-morning dose and 0 (pre-dose) and 2 hours post-midday dose on Day 2 of Week 1 and Day 2 of Week 6
Population: All enrolled participants who received at least 1 dose of study drug (As-Treated Population) and had evaluable prednisone or deflazacort plasma data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | Pre-Dose, Prednisone, Week 1 | 1.01 ng/mL | Standard Deviation 0 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 30 minutes Post-Dose, Prednisone, Week 1 | 18.27 ng/mL | Standard Deviation 14.451 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 1 hour Post-Dose, Prednisone, Week 1 | 35.48 ng/mL | Standard Deviation 24.026 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 2 hours Post-Dose, Prednisone, Week 1 | 32.41 ng/mL | Standard Deviation 27.603 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 3 hours Post-Dose, Prednisone, Week 1 | 57.12 ng/mL | Standard Deviation 6.948 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 4 hours Post-Dose, Prednisone, Week 1 | 49.44 ng/mL | Standard Deviation 12.139 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 6 hours Post-Dose, Prednisone, Week 1 | 31.41 ng/mL | Standard Deviation 12.367 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 8 hours Post-Dose, Prednisone, Week 1 | 15.59 ng/mL | Standard Deviation 8.735 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | Pre-Dose, Prednisone, Week 6 | 1.01 ng/mL | Standard Deviation 0 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 30 minutes Post-Dose, Prednisone, Week 6 | 17.13 ng/mL | Standard Deviation 16.376 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 1 hour Post-Dose, Prednisone, Week 6 | 32.48 ng/mL | Standard Deviation 21.19 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 2 hours Post-Dose, Prednisone, Week 6 | 39.91 ng/mL | Standard Deviation 26.374 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 3 hours Post-Dose, Prednisone, Week 6 | 41.02 ng/mL | Standard Deviation 13.444 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 4 hours Post-Dose, Prednisone, Week 6 | 38.82 ng/mL | Standard Deviation 5.934 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 6 hours Post-Dose, Prednisone, Week 6 | 24.95 ng/mL | Standard Deviation 14.243 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 8 hours Post-Dose, Prednisone, Week 6 | 13.52 ng/mL | Standard Deviation 11.872 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | Pre-Dose, Deflazacort, Week 1 | 0 ng/mL | Standard Deviation 0 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 30 minutes Post-Dose, Deflazacort, Week 1 | 28.25 ng/mL | Standard Deviation 31.968 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 1 hours Post-Dose, Deflazacort, Week 1 | 49.47 ng/mL | Standard Deviation 43.631 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 2 hours Post-Dose, Deflazacort, Week 1 | 74.00 ng/mL | Standard Deviation 49.349 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 3 hours Post-Dose, Deflazacort, Week 1 | 63.34 ng/mL | Standard Deviation 38.045 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 4 hours Post-Dose, Deflazacort, Week 1 | 45.50 ng/mL | Standard Deviation 31.427 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 6 hours Post-Dose, Deflazacort, Week 1 | 18.67 ng/mL | Standard Deviation 17.648 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 8 hours Post-Dose, Deflazacort, Week 1 | 7.57 ng/mL | Standard Deviation 9.418 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | Pre-Dose, Deflazacort, Week 6 | 0.06 ng/mL | Standard Deviation 0.268 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 30 minutes Post-Dose, Deflazacort, Week 6 | 33.46 ng/mL | Standard Deviation 32.511 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 1 hour Post-Dose, Deflazacort, Week 6 | 71.94 ng/mL | Standard Deviation 77.37 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 2 hours Post-Dose, Deflazacort, Week 6 | 81.41 ng/mL | Standard Deviation 44.945 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 3 hours Post-Dose, Deflazacort, Week 6 | 49.63 ng/mL | Standard Deviation 26.633 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 4 hours Post-Dose, Deflazacort, Week 6 | 25.85 ng/mL | Standard Deviation 16.126 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 6 hours Post-Dose, Deflazacort, Week 6 | 10.14 ng/mL | Standard Deviation 14.08 |
| Ataluren | Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort | 8 hours Post-Dose, Deflazacort, Week 6 | 4.15 ng/mL | Standard Deviation 7.985 |
Secondary
Pharmacokinetics: Ataluren Plasma Exposure in All Participants
Blood for ataluren concentrations over a 24-hour period was to be collected on Day 2 of Week 1 and Day 2 of Week 6. Analysis of the blood samples was to be conducted 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/milliliters (μg/mL). Plasma concentrations below qualification (BQ) is treated as 0 in the summary calculation.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, and 4 hours post-morning dose and 0 (pre-dose) and 2 hours post-midday dose on Day 2 of Week 1 and Day 2 of Week 6
Population: All enrolled participants who received at least 1 dose of study drug (As-Treated Population) and had evaluable plasma data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | Pre-Morning Dose, Week 1 | 0 μg/mL | Standard Deviation 0 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | 30 minutes Post-Morning Dose, Week 1 | 14.59 μg/mL | Standard Deviation 10.404 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | 1 hour Post-Morning Dose, Week 1 | 16.24 μg/mL | Standard Deviation 10.251 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | 2 hours Post-Morning Dose, Week 1 | 23.71 μg/mL | Standard Deviation 12.895 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | 3 hours Post-Dose, Week 1 | 28.96 μg/mL | Standard Deviation 15.306 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | 4 hours Post-Morning Dose, Week 1 | 29.44 μg/mL | Standard Deviation 14.854 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | Pre-Midday Dose, Week 1 | 20.43 μg/mL | Standard Deviation 15.256 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | 2 hours Post-Midday Dose, Week 1 | 35.00 μg/mL | Standard Deviation 17.172 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | Pre-Morning Dose, Week 6 | 19.99 μg/mL | Standard Deviation 15.598 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | 30 minutes Post-Morning Dose, Week 6 | 24.50 μg/mL | Standard Deviation 17.916 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | 1 hour Post-Morning Dose, Week 6 | 24.68 μg/mL | Standard Deviation 19.577 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | 2 hours Post-Morning Dose, Week 6 | 26.79 μg/mL | Standard Deviation 18.709 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | 3 hours Post-Morning Dose, Week 6 | 26.40 μg/mL | Standard Deviation 16.961 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | 4 hours Post-Morning Dose, Week 6 | 24.04 μg/mL | Standard Deviation 17.641 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | Pre-Midday Dose, Week 6 | 17.15 μg/mL | Standard Deviation 13.19 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in All Participants | 2 hours Post-Midday Dose, Week 6 | 25.49 μg/mL | Standard Deviation 14.297 |
Secondary
Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants
Blood for ataluren concentrations were collected on Day 2 of Week 1 and Day 2 of Week 6. Analysis of the blood samples was to be conducted using a validated HPLC-MS/MS method with a LLOQ of 0.5 μg/mL. Plasma concentrations BQ is treated as 0 in the summary calculation.
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, and 4 hours post-morning dose and 0 (pre-dose) and 2 hours post-midday dose on Day 2 of Week 1 and Day 2 of Week 6
Population: All enrolled participants who received at least 1 dose of study drug, were ambulatory, and had evaluable plasma data. Participants who were ambulatory were able to walk ≥75 meters unassisted at screening.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | 2 hours Post-Midday Dose, Week 6 | 21.09 μg/mL | Standard Deviation 7.959 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | Pre-Morning Dose, Week 1 | 0 μg/mL | Standard Deviation 0 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | 30 minutes Post-Morning Dose, Week 1 | 14.88 μg/mL | Standard Deviation 10.771 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | 1 hour Post-Morning Dose, Week 1 | 14.65 μg/mL | Standard Deviation 9.608 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | 2 hours Post-Morning Dose, Week 1 | 20.96 μg/mL | Standard Deviation 12.648 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | 3 hours Post-Dose, Week 1 | 26.29 μg/mL | Standard Deviation 15.853 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | 4 hours Post-Morning Dose, Week 1 | 26.19 μg/mL | Standard Deviation 14.531 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | Pre-Midday Dose, Week 1 | 15.26 μg/mL | Standard Deviation 10.238 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | 2 hours Post-Midday Dose, Week 1 | 32.08 μg/mL | Standard Deviation 17.977 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | Pre-Morning Dose, Week 6 | 14.83 μg/mL | Standard Deviation 10.032 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | 30 minutes Post-Morning Dose, Week 6 | 18.08 μg/mL | Standard Deviation 8.654 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | 1 hour Post-Morning Dose, Week 6 | 17.75 μg/mL | Standard Deviation 8.66 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | 2 hours Post-Morning Dose, Week 6 | 20.33 μg/mL | Standard Deviation 9.103 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | 3 hours Post-Morning Dose, Week 6 | 20.13 μg/mL | Standard Deviation 9.423 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | 4 hours Post-Morning Dose, Week 6 | 18.72 μg/mL | Standard Deviation 12.255 |
| Ataluren | Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants | Pre-Midday Dose, Week 6 | 12.40 μg/mL | Standard Deviation 6.775 |
Secondary
Study Drug Compliance
Study drug compliance was assessed by the participant daily diary and quantification of used and unused study drug. Compliance was assessed in terms of the amount of drug actually taken relative to the amount that was prescribed. Physician-prescribed dose reductions and interruptions were factored into the calculations. Not recorded applies only to the days on which all dosing information was missing or for missing days. Invalid entries in the participant daily diary were assigned values of 0.0 for percentage of doses taken and 99.0 for percentage of doses not recorded.
Time frame: Baseline up to Week 89
Population: All enrolled participants who received at least 1 dose of study drug (As-Treated Population).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ataluren | Study Drug Compliance | Percentage of Doses Taken as Planned | 84.7 percentage of doses of study drug |
| Ataluren | Study Drug Compliance | Percentage of Doses Missed | 1.1 percentage of doses of study drug |
| Ataluren | Study Drug Compliance | Percentage of Doses Changed | 0.3 percentage of doses of study drug |
| Ataluren | Study Drug Compliance | Percentage of Doses Not Recorded | 10.2 percentage of doses of study drug |