Phase 2a Extension Study of Ataluren (PTC124) in Duchenne Muscular Dystrophy (DMD)

• Sponsor: PTC Therapeutics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00759876
• Collaborator: Genzyme, a Sanofi Company (Industry)
• Enrollment: 36
• Locations: 3
• Arm: 1
• Actual Duration (Months): 21.1
• Patients Per Site: 12
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy	Drug: Ataluren	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2a Extension Study of PTC124 in Subjects With Nonsense-Mutation-Mediated Duchenne Muscular Dystrophy
• Actual Study Start Date: Aug 13, 2008
• Actual Primary Completion Date: May 17, 2010
• Actual Study Completion Date: May 17, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ataluren Participants will receive ataluren 3 times per day with meals at doses of 20 milligrams per kilogram (mg/kg) (breakfast), 20 mg/kg (lunch), and 40 mg/kg (dinner) for up to 89 weeks.	Drug: Ataluren; Ataluren will be provided as a vanilla-flavored powder to be mixed with milk. Dosing based on participant body weight; Other Names: PTC124

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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).

3. 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).

4. 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).

5. 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).

6. 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).

7. 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).

8. 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.

9. 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.

10. 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.

11. 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.

12. 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).

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Male
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
2	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
3	University of Utah	Salt Lake City	Utah	United States	84112

Sponsors and Collaborators

• PTC Therapeutics
• Genzyme, a Sanofi Company

Investigators

• Study Director: Leone Atkinson, PTC Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

• Hirawat S, Welch EM, Elfring GL, Northcutt VJ, Paushkin S, Hwang S, Leonard EM, Almstead NG, Ju W, Peltz SW, Miller LL. Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers. J Clin Pharmacol. 2007 Apr;47(4):430-44.
• Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ, Trifillis P, Paushkin S, Patel M, Trotta CR, Hwang S, Wilde RG, Karp G, Takasugi J, Chen G, Jones S, Ren H, Moon YC, Corson D, Turpoff AA, Campbell JA, Conn MM, Khan A, Almstead NG, Hedrick J, Mollin A, Risher N, Weetall M, Yeh S, Branstrom AA, Colacino JM, Babiak J, Ju WD, Hirawat S, Northcutt VJ, Miller LL, Spatrick P, He F, Kawana M, Feng H, Jacobson A, Peltz SW, Sweeney HL. PTC124 targets genetic disorders caused by nonsense mutations. Nature. 2007 May 3;447(7140):87-91. Epub 2007 Apr 22.

• Responsible Party: PTC Therapeutics
• ClinicalTrials.gov Identifier: NCT00759876
• Other Study ID Numbers: PTC124-GD-004e-DMD
• First Posted: Sep 25, 2008
• Last Update Posted: Oct 29, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by PTC Therapeutics: Duchenne muscular dystrophy; Nonsense mutation; Premature stop codon; DMD; PTC124; Ataluren
• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne

Study Results

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 Detail	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.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Period Title: Overall Study
STARTED	36
As-Treated Population	36
Evaluable Population	35
Ambulatory Evaluable Population	24
COMPLETED	0
NOT COMPLETED	36

Baseline Characteristics

Arm/Group Title	Ataluren
Arm/Group Description	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.
Overall Participants	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	11.6 (2.61)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	36 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description	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

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug (As-Treated Population).

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	36
At least 1 TEAE	36 100%
Mild TEAE	9 25%
Moderate TEAE	16 44.4%
Severe TEAE	10 27.8%
Life-Threatening TEAE	1 2.8%
Fatal TEAE	0 0%
Related TEAE	28 77.8%
Serious TEAE	6 16.7%

2. Secondary Outcome

Title	Change From Baseline in 6-Minute Walk Distance (6MWD) as Measured by the 6-minute Walk Test (6MWT)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	23
Baseline	367.8 (107.3)
Change from Baseline at Week 48	-80.4 (59.5)
Change from Baseline at Week 60	-101.5 (64.4)

3. Secondary Outcome

Title	Change From Baseline in Proximal Muscle Function as Assessed by Speed During Timed Function Tests
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	24
Rise to Standing, Baseline	13.57 (11.111)
Rise to Standing, Change from Baseline at Week 48	6.49 (8.059)
Rise to Standing, Change from Baseline at Week 60	5.77 (7.790)
Walk/Run 10 m, Baseline	7.62 (3.641)
Walk/Run 10 m, Change from Baseline at Week 48	3.15 (5.591)
Walk/Run 10 m, Change from Baseline at Week 60	3.20 (5.930)
Ascend 4 Stairs, Baseline	7.16 (7.481)
Ascend 4 Stairs, Change from Baseline at Week 48	4.92 (6.856)
Ascend 4 Stairs, Change from Baseline at Week 60	6.30 (7.926)
Descend 4 Stairs, Baseline	6.42 (7.565)
Descend 4 Stairs, Change from Baseline at Week 48	5.25 (8.839)
Descend 4 Stairs, Change from Baseline at Week 60	4.28 (7.275)

4. Secondary Outcome

Title	Change From Baseline in Standing From Supine Position as Assessed by Method Scores During Timed Function Tests
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	24
Baseline	3.25 (1.260)
Change from Baseline at Week 48	-0.58 (0.929)
Change from Baseline at Week 60	-0.62 (0.921)

5. Secondary Outcome

Title	Change From Baseline in Run/Walk 10-Meters as Assessed by Method Scores During Timed Function Tests
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	24
Baseline	4.42 (0.974)
Change from Baseline at Week 48	-0.25 (1.073)
Change from Baseline at Week 60	-0.57 (1.207)

6. Secondary Outcome

Title	Change From Baseline in Ascending 4 Stairs as Assessed by Method Scores During Timed Function Tests
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	24
Baseline	3.58 (1.717)
Change from Baseline at Week 48	-0.46 (1.141)
Change from Baseline at Week 60	-0.48 (1.365)

7. Secondary Outcome

Title	Change From Baseline in Descending 4 Stairs as Assessed by Method Scores During Timed Function Tests
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	24
Baseline	3.63 (1.740)
Change from Baseline at Week 48	-0.04 (1.160)
Change from Baseline at Week 60	-0.10 (0.889)

8. Secondary Outcome

Title	Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, Shoulder Abduction, and Hand Grip as Assessed by Myometry
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	35
Left (L) Knee Flexion, Baseline	9.48 (4.395)
L Knee Flexion, Change from Baseline at Wk 48	1.23 (2.715)
L Knee Flexion, Change from Baseline at Wk 60	0.64 (3.079)
Right (R) Knee Flexion, Baseline	10.15 (5.439)
R Knee Flexion, Change from Baseline at Wk 48	0.81 (2.254)
R Knee Flexion, Change from Baseline at Wk 60	-0.05 (2.240)
L Knee Extension, Baseline	8.63 (5.124)
L Knee Extension, Change from Baseline at Wk 48	-1.07 (1.842)
L Knee Extension, Change from Baseline at Wk 60	-1.00 (1.567)
R Knee Extension, Baseline	9.10 (6.109)
R Knee Extension, Change from Baseline at Wk 48	-1.33 (2.021)
R Knee Extension, Change from Baseline at Wk 60	-1.65 (2.204)
L Elbow Flexion, Baseline	5.70 (3.611)
L Elbow Flexion, Change from Baseline at Wk 48	-0.15 (0.998)
L Elbow Flexion, Change from Baseline at Wk 60	-0.51 (1.121)
R Elbow Flexion, Baseline	5.85 (3.758)
R Elbow Flexion, Change from Baseline at Wk 48	-0.28 (1.050)
R Elbow Flexion, Change from Baseline at Wk 60	-0.55 (1.061)
L Elbow Extension, Baseline	4.55 (2.322)
L Elbow Extension, Change from Baseline at Wk 48	-0.10 (0.993)
L Elbow Extension, Change from Baseline at Wk 60	-0.32 (0.818)
R Elbow Extension, Baseline	4.89 (2.680)
R Elbow Extension, Change from Baseline at Wk 48	-0.10 (1.600)
R Elbow Extension, Change from Baseline at Wk 60	-0.60 (1.352)
L Shoulder Abduction, Baseline	4.29 (2.783)
L Shoulder Abduction Change from Baseline at Wk 48	-0.90 (0.906)
L Shoulder Abduction Change from Baseline at Wk 60	-1.10 (1.632)
R Shoulder Abduction, Baseline	4.39 (2.666)
R Shoulder Abduction Change from Baseline at Wk 48	-1.02 (1.369)
R Shoulder Abduction Change from Baseline at Wk 60	-1.23 (1.888)
L Hand Grip, Baseline	15.19 (5.881)
L Hand Grip, Change from Baseline at Wk 48	0.30 (3.353)
L Hand Grip, Change from Baseline at Wk 60	1.04 (4.811)
R Hand Grip, Baseline	17.17 (7.266)
R Hand Grip, Change from Baseline at Wk 48	-0.79 (3.628)
R Hand Grip, Change from Baseline at Wk 60	-0.61 (3.010)

9. Secondary Outcome

Title	Change in Resting, Active, and Recovery Heart Rate as Assessed by Heart Rate Monitoring With the Polar RS400
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	24
Resting Heart Rate, Baseline	106.46 (11.163)
Resting Heart Rate, Change from Baseline at Wk 48	8.30 (12.382)
Resting Heart Rate, Change from Baseline at Wk 60	5.16 (11.197)
Active Heart Rate, Baseline	152.17 (13.457)
Active Heart Rate, Change from Baseline at Wk 48	3.86 (12.365)
Active Heart Rate, Change from Baseline at Wk 60	-2.84 (17.238)
Recovery Heart Rate, Baseline	113.13 (12.664)
Recovery Heart Rate, Change from Baseline at Wk 48	4.64 (9.079)
Recovery Heart Rate, Change from Baseline at Wk 60	1.68 (15.688)

10. Secondary Outcome

Title	Change From Baseline in Verbal Memory and Attention as Assessed by the Digit Span Task
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	35
Recalled Forward, Baseline	3.66 (2.378)
Recalled Forward, Change from Baseline at Wk 48	0.14 (1.353)
Recalled Forward, Change from Baseline at Wk 60	0.04 (1.453)
Recalled Backward, Baseline	3.15 (2.524)
Recalled Backward, Change from Baseline at Wk 48	0.74 (1.442)
Recalled Backward, Change from Baseline at Wk 60	0.74 (1.442)

11. Secondary Outcome

Title	Change From Baseline in Participant-Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	35
Physical Functioning, Baseline	45.13 (21.114)
Physical Functioning Change from Baseline at Wk 48	3.16 (20.180)
Physical Functioning Change from Baseline at Wk 60	6.25 (23.545)
Emotional Functioning, Baseline	65.29 (16.141)
Emotional Function, Change from Baseline at Wk 48	8.24 (18.294)
Emotional Function, Change from Baseline at Wk 60	12.22 (17.614)
Social Functioning, Baseline	61.80 (16.914)
Social Functioning, Change from Baseline at Wk 48	4.82 (19.463)
Social Functioning, Change from Baseline at Wk 60	3.75 (15.861)
School Functioning, Baseline	70.29 (16.466)
School Functioning, Change from Baseline at Wk 48	1.76 (17.917)
School Functioning, Change from Baseline at Wk 60	3.29 (16.273)
Fatigue Scale Score, Baseline	74.28 (14.917)
Fatigue Scale Score, Change from Baseline at Wk 48	5.08 (12.661)
Fatigue Scale Score, Change from Baseline at Wk 60	4.39 (11.777)
Total Score, Baseline	58.59 (12.793)
Total Score, Change from Baseline at Wk 48	4.28 (13.406)
Total Score, Change from Baseline at Wk 60	6.42 (10.887)

12. Secondary Outcome

Title	Change From Baseline in Parent- or Caregiver-Reported HRQL as Measured by the PedsQL Inventory
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	35
Physical Functioning, Baseline	48.07 (21.111)
Physical Functioning Change from Baseline at Wk 48	2.31 (20.284)
Physical Functioning Change from Baseline at Wk 60	1.85 (19.366)
Emotional Functioning, Baseline	69.45 (17.465)
Emotional Function, Change from Baseline at Wk 48	5.27 (19.595)
Emotional Function, Change from Baseline at Wk 60	3.29 (20.021)
Social Functioning, Baseline	57.95 (19.397)
Social Functioning, Change from Baseline at Wk 48	9.38 (16.956)
Social Functioning, Change from Baseline at Wk 60	6.16 (17.599)
School Functioning, Baseline	67.61 (14.944)
School Functioning, Change from Baseline at Wk 48	5.66 (15.824)
School Functioning, Change from Baseline at Wk 60	-0.37 (10.651)
Fatigue Scale Score, Baseline	72.25 (13.777)
Fatigue Scale Score, Change from Baseline at Wk 48	0.77 (9.703)
Fatigue Scale Score, Change from Baseline at Wk 60	-0.40 (9.269)
Total Score, Baseline	59.08 (13.348)
Total Score, Change from Baseline at Wk 48	5.24 (11.409)
Total Score, Change from Baseline at Wk 60	2.68 (12.261)

13. Secondary Outcome

Title	Change From Baseline in Serum Creatine Kinase (CK) Levels
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	35
Baseline	5988.31 (3967.714)
Change from Baseline at Week 48	84.06 (2641.422)
Change from Baseline at Week 60	-549.57 (3261.151)

14. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug (As-Treated Population) and had evaluable dystrophin expression data.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	36
Baseline	16.828 (8.4285)
Change from Baseline	-1.880 (5.1337)

15. Secondary Outcome

Title	Study Drug Compliance
Description	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

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug (As-Treated Population).

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	36
Percentage of Doses Taken as Planned	84.7
Percentage of Doses Missed	1.1
Percentage of Doses Changed	0.3
Percentage of Doses Not Recorded	10.2

16. Secondary Outcome

Title	Pharmacokinetics: Ataluren Plasma Exposure in All Participants
Description	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

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug (As-Treated Population) and had evaluable plasma data.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	36
Pre-Morning Dose, Week 1	0 (0)
30 minutes Post-Morning Dose, Week 1	14.59 (10.404)
1 hour Post-Morning Dose, Week 1	16.24 (10.251)
2 hours Post-Morning Dose, Week 1	23.71 (12.895)
3 hours Post-Dose, Week 1	28.96 (15.306)
4 hours Post-Morning Dose, Week 1	29.44 (14.854)
Pre-Midday Dose, Week 1	20.43 (15.256)
2 hours Post-Midday Dose, Week 1	35.00 (17.172)
Pre-Morning Dose, Week 6	19.99 (15.598)
30 minutes Post-Morning Dose, Week 6	24.50 (17.916)
1 hour Post-Morning Dose, Week 6	24.68 (19.577)
2 hours Post-Morning Dose, Week 6	26.79 (18.709)
3 hours Post-Morning Dose, Week 6	26.40 (16.961)
4 hours Post-Morning Dose, Week 6	24.04 (17.641)
Pre-Midday Dose, Week 6	17.15 (13.190)
2 hours Post-Midday Dose, Week 6	25.49 (14.297)

17. Secondary Outcome

Title	Pharmacokinetics: Ataluren Plasma Exposure in Ambulatory Participants
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	25
Pre-Morning Dose, Week 1	0 (0)
30 minutes Post-Morning Dose, Week 1	14.88 (10.771)
1 hour Post-Morning Dose, Week 1	14.65 (9.608)
2 hours Post-Morning Dose, Week 1	20.96 (12.648)
3 hours Post-Dose, Week 1	26.29 (15.853)
4 hours Post-Morning Dose, Week 1	26.19 (14.531)
Pre-Midday Dose, Week 1	15.26 (10.238)
2 hours Post-Midday Dose, Week 1	32.08 (17.977)
Pre-Morning Dose, Week 6	14.83 (10.032)
30 minutes Post-Morning Dose, Week 6	18.08 (8.654)
1 hour Post-Morning Dose, Week 6	17.75 (8.660)
2 hours Post-Morning Dose, Week 6	20.33 (9.103)
3 hours Post-Morning Dose, Week 6	20.13 (9.423)
4 hours Post-Morning Dose, Week 6	18.72 (12.255)
Pre-Midday Dose, Week 6	12.40 (6.775)
2 hours Post-Midday Dose, Week 6	21.09 (7.959)

18. Secondary Outcome

Title	Corticosteroid Plasma Concentrations as Assessed by a Validated Bioanalytical Method, in Participants Who Received a Daily Corticosteroid Regimen With Prednisone or Deflazacort
Description	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

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug (As-Treated Population) and had evaluable prednisone or deflazacort plasma data.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	36
Pre-Dose, Prednisone, Week 1	1.01 (0)
30 minutes Post-Dose, Prednisone, Week 1	18.27 (14.451)
1 hour Post-Dose, Prednisone, Week 1	35.48 (24.026)
2 hours Post-Dose, Prednisone, Week 1	32.41 (27.603)
3 hours Post-Dose, Prednisone, Week 1	57.12 (6.948)
4 hours Post-Dose, Prednisone, Week 1	49.44 (12.139)
6 hours Post-Dose, Prednisone, Week 1	31.41 (12.367)
8 hours Post-Dose, Prednisone, Week 1	15.59 (8.735)
Pre-Dose, Prednisone, Week 6	1.01 (0)
30 minutes Post-Dose, Prednisone, Week 6	17.13 (16.376)
1 hour Post-Dose, Prednisone, Week 6	32.48 (21.190)
2 hours Post-Dose, Prednisone, Week 6	39.91 (26.374)
3 hours Post-Dose, Prednisone, Week 6	41.02 (13.444)
4 hours Post-Dose, Prednisone, Week 6	38.82 (5.934)
6 hours Post-Dose, Prednisone, Week 6	24.95 (14.243)
8 hours Post-Dose, Prednisone, Week 6	13.52 (11.872)
Pre-Dose, Deflazacort, Week 1	0 (0)
30 minutes Post-Dose, Deflazacort, Week 1	28.25 (31.968)
1 hours Post-Dose, Deflazacort, Week 1	49.47 (43.631)
2 hours Post-Dose, Deflazacort, Week 1	74.00 (49.349)
3 hours Post-Dose, Deflazacort, Week 1	63.34 (38.045)
4 hours Post-Dose, Deflazacort, Week 1	45.50 (31.427)
6 hours Post-Dose, Deflazacort, Week 1	18.67 (17.648)
8 hours Post-Dose, Deflazacort, Week 1	7.57 (9.418)
Pre-Dose, Deflazacort, Week 6	0.06 (0.268)
30 minutes Post-Dose, Deflazacort, Week 6	33.46 (32.511)
1 hour Post-Dose, Deflazacort, Week 6	71.94 (77.370)
2 hours Post-Dose, Deflazacort, Week 6	81.41 (44.945)
3 hours Post-Dose, Deflazacort, Week 6	49.63 (26.633)
4 hours Post-Dose, Deflazacort, Week 6	25.85 (16.126)
6 hours Post-Dose, Deflazacort, Week 6	10.14 (14.080)
8 hours Post-Dose, Deflazacort, Week 6	4.15 (7.985)

19. Secondary Outcome

Title	Change in Muscle Composition as Assessed by Limb Magnetic Resonance (MR) Testing
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	0

Adverse Events

Time Frame	Baseline up to Week 89
Adverse Event Reporting Description	All enrolled participants who received at least 1 dose of study drug (As-Treated Population).
Arm/Group Title	Ataluren
Arm/Group Description	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.
All Cause Mortality
	Ataluren
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ataluren
	Affected / at Risk (%)	# Events
Total	6/36 (16.7%)
Infections and infestations
Influenza	1/36 (2.8%)	1
Pneumonia	1/36 (2.8%)	1
Injury, poisoning and procedural complications
Femur fracture	1/36 (2.8%)	1
Musculoskeletal and connective tissue disorders
Muscle contracture	1/36 (2.8%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/36 (2.8%)	1
Vascular disorders
Hypertension	2/36 (5.6%)	2
Other (Not Including Serious) Adverse Events
	Ataluren
	Affected / at Risk (%)	# Events
Total	36/36 (100%)
Cardiac disorders
Myocardial fibrosis	2/36 (5.6%)
Tachycardia	2/36 (5.6%)
Gastrointestinal disorders
Abdominal pain	6/36 (16.7%)
Abdominal pain upper	11/36 (30.6%)
Constipation	3/36 (8.3%)
Diarrhoea	8/36 (22.2%)
Flatulence	12/36 (33.3%)
Nausea	3/36 (8.3%)
Stomach discomfort	3/36 (8.3%)
Vomiting	24/36 (66.7%)
General disorders
Asthenia	3/36 (8.3%)
Disease progression	4/36 (11.1%)
Gait disturbance	4/36 (11.1%)
Pyrexia	7/36 (19.4%)
Infections and infestations
Bronchitis	4/36 (11.1%)
Gastroenteritis	2/36 (5.6%)
Gastroenteritis viral	2/36 (5.6%)
Influenza	5/36 (13.9%)
Localized Infections	2/36 (5.6%)
Nasopharyngitis	3/36 (8.3%)
Otitis media	2/36 (5.6%)
Rhinitis	4/36 (11.1%)
Sinusitis	2/36 (5.6%)
Upper respiratory tract infection	10/36 (27.8%)
Injury, poisoning and procedural complications
Contusion	7/36 (19.4%)
Excoriation	3/36 (8.3%)
Fall	11/36 (30.6%)
Head injury	3/36 (8.3%)
Iliotibial band syndrome	2/36 (5.6%)
Joint injury	5/36 (13.9%)
Joint sprain	5/36 (13.9%)
Limb injury	2/36 (5.6%)
Postprocedural discomfort	9/36 (25%)
Procedural pain	4/36 (11.1%)
Spinal compression fracture	2/36 (5.6%)
Investigations
Weight decreased	5/36 (13.9%)
Metabolism and nutrition disorders
Decreased appetite	2/36 (5.6%)
Insulin resistance	3/36 (8.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/36 (13.9%)
Back pain	6/36 (16.7%)
Groin pain	2/36 (5.6%)
Joint contracture	5/36 (13.9%)
Muscular weakness	9/36 (25%)
Musculoskeletal pain	2/36 (5.6%)
Myalgia	4/36 (11.1%)
Pain in extremity	6/36 (16.7%)
Scoliosis	5/36 (13.9%)
Tendinous contracture	3/36 (8.3%)
Nervous system disorders
Headache	17/36 (47.2%)
Migraine	4/36 (11.1%)
Motor dysfunction	3/36 (8.3%)
Renal and urinary disorders
Haematuria	2/36 (5.6%)
Urinary incontinence	3/36 (8.3%)
Respiratory, thoracic and mediastinal disorders
Apnoea	2/36 (5.6%)
Cough	14/36 (38.9%)
Dyspnoea	2/36 (5.6%)
Epistaxis	2/36 (5.6%)
Nasal congestion	11/36 (30.6%)
Oropharyngeal pain	6/36 (16.7%)
Respiratory tract congestion	4/36 (11.1%)
Rhinorrhoea	2/36 (5.6%)
Sinus congestion	5/36 (13.9%)
Sleep apnoea syndrome	2/36 (5.6%)
Upper respiratory tract congestion	3/36 (8.3%)
Skin and subcutaneous tissue disorders
Dermatitis contact	2/36 (5.6%)
Erythema	2/36 (5.6%)
Rash	6/36 (16.7%)
Urticaria	3/36 (8.3%)
Vascular disorders
Flushing	2/36 (5.6%)
Hypertension	2/36 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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