Trial Outcomes & Findings for Phase 2B Study of PTC124 (Ataluren) in Duchenne/Becker Muscular Dystrophy (DMD/BMD) (NCT NCT00592553)

Last Updated: 2020-04-07

Results Overview

The 6MWD test was performed in a 30 meters long flat corridor, where the participant was instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures by measuring the 6MWD in meters. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

174 participants

Primary outcome timeframe

Baseline, Week 48

Results posted on

2020-04-07

Participant Flow

A total of 185 participants were screened for eligibility, of which 11 participants did not meet entry criteria.

A total of 174 eligible participants were randomized in 1:1:1 ratio to receive either placebo, low-dose ataluren, or high-dose ataluren.

Participant milestones

Participant milestones
Measure	High-Dose Ataluren Participants received ataluren suspension orally 3 times a day (TID), 20 milligrams/kilogram (mg/kg) at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Overall Study STARTED	60	57	57
Overall Study As-treated Population	60	57	57
Overall Study ITT Population	60	57	57
Overall Study COMPLETED	59	57	57
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	High-Dose Ataluren Participants received ataluren suspension orally 3 times a day (TID), 20 milligrams/kilogram (mg/kg) at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Overall Study Protocol Noncompliance	1	0	0

Baseline Characteristics

Phase 2B Study of PTC124 (Ataluren) in Duchenne/Becker Muscular Dystrophy (DMD/BMD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Total n=174 Participants Total of all reporting groups
Age, Continuous	8.4 years STANDARD_DEVIATION 2.53 • n=5 Participants	8.8 years STANDARD_DEVIATION 2.91 • n=7 Participants	8.3 years STANDARD_DEVIATION 2.33 • n=5 Participants	8.5 years STANDARD_DEVIATION 2.59 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	60 Participants n=5 Participants	57 Participants n=7 Participants	57 Participants n=5 Participants	174 Participants n=4 Participants
6-Minute Walk Distance (6MWD)	358.2 meters STANDARD_DEVIATION 103.97 • n=5 Participants	350.0 meters STANDARD_DEVIATION 97.55 • n=7 Participants	359.6 meters STANDARD_DEVIATION 87.67 • n=5 Participants	356.0 meters STANDARD_DEVIATION 96.30 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 48

Population: Intent-to-treat (ITT) population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=59 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=55 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=55 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in 6MWD at Week 48	-41.81 meters Standard Deviation 89.234	-12.86 meters Standard Deviation 72.007	-42.56 meters Standard Deviation 90.046

SECONDARY outcome

Timeframe: Baseline, Week 48

Population: ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable at specified timepoint.

If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. Change from baseline data has been reported.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Time to Stand From Supine Position at Week 48 Baseline	12.25 seconds Standard Deviation 11.191	10.80 seconds Standard Deviation 9.924	11.50 seconds Standard Deviation 11.440
Change From Baseline in Time to Stand From Supine Position at Week 48 Change at Week 48	3.00 seconds Standard Deviation 5.686	3.23 seconds Standard Deviation 5.761	3.24 seconds Standard Deviation 7.253

SECONDARY outcome

Timeframe: Baseline, Week 48

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Time to Walk/Run 10 Meters at Week 48 Baseline	7.80 seconds Standard Deviation 5.243	7.45 seconds Standard Deviation 4.373	6.86 seconds Standard Deviation 2.813
Change From Baseline in Time to Walk/Run 10 Meters at Week 48 Change at Week 48	2.37 seconds Standard Deviation 6.149	1.68 seconds Standard Deviation 5.617	3.03 seconds Standard Deviation 6.691

SECONDARY outcome

Timeframe: Baseline, Week 48

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Time to Climb 4 Stairs at Week 48 Change at Week 48	3.51 seconds Standard Deviation 6.794	2.39 seconds Standard Deviation 4.618	4.79 seconds Standard Deviation 7.949
Change From Baseline in Time to Climb 4 Stairs at Week 48 Baseline	7.63 seconds Standard Deviation 7.522	6.94 seconds Standard Deviation 6.474	6.04 seconds Standard Deviation 5.661

SECONDARY outcome

Timeframe: Baseline, Week 48

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Time to Descend 4 Stairs at Week 48 Baseline	6.75 seconds Standard Deviation 7.219	6.08 seconds Standard Deviation 5.985	5.52 seconds Standard Deviation 5.753
Change From Baseline in Time to Descend 4 Stairs at Week 48 Change at Week 48	2.95 seconds Standard Deviation 7.323	2.41 seconds Standard Deviation 6.162	4.03 seconds Standard Deviation 7.828

SECONDARY outcome

Timeframe: Baseline, Week 48

Upper and lower extremity myometry was performed using a myometer following standardized procedures. Muscle groups evaluated included knee flexors, knee extensors, elbow flexors, elbow extensors, and shoulder abductors. Bilateral assessments were done and 3 measurements were recorded from each muscle group on each side if possible. Mean values for the left and right sides were calculated.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry Baseline: Force during knee flexion	12.45 pounds Standard Deviation 4.684	12.08 pounds Standard Deviation 4.217	11.06 pounds Standard Deviation 3.494
Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry Change at Week 48: Force during knee flexion	0.39 pounds Standard Deviation 3.148	-0.07 pounds Standard Deviation 3.511	0.38 pounds Standard Deviation 2.991
Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry Baseline: Force during knee extension	12.71 pounds Standard Deviation 7.910	12.81 pounds Standard Deviation 5.753	12.96 pounds Standard Deviation 6.162
Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry Change at Week 48: Force during knee extension	-0.59 pounds Standard Deviation 3.511	-0.63 pounds Standard Deviation 3.616	-1.85 pounds Standard Deviation 3.899
Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry Baseline: Force exerted during elbow flexion	8.72 pounds Standard Deviation 4.709	7.66 pounds Standard Deviation 3.154	8.14 pounds Standard Deviation 2.972
Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry Change at Week 48: Force during elbow flexion	-0.50 pounds Standard Deviation 1.832	-0.10 pounds Standard Deviation 1.680	-0.35 pounds Standard Deviation 1.807
Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry Baseline: Force during elbow extension	6.81 pounds Standard Deviation 3.815	6.19 pounds Standard Deviation 3.083	6.77 pounds Standard Deviation 2.785
Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry Change at Week 48: Force during elbow extension	-0.28 pounds Standard Deviation 1.473	0.10 pounds Standard Deviation 1.493	-0.51 pounds Standard Deviation 2.333

SECONDARY outcome

Timeframe: Baseline, Week 48

The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean activity period/day/visit was computed for each participant. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as the first time after 3:00 AM that greater than (\>) 2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was less than (\<) 50 percent (%) of the mean active period across all days for that participant's visit.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Mean Activity Period/Day/Visit at Week 48, as Assessed by Step Activity Monitoring (SAM) Baseline	756.84 minutes Standard Deviation 84.612	761.86 minutes Standard Deviation 76.984	751.71 minutes Standard Deviation 60.513
Change From Baseline in Mean Activity Period/Day/Visit at Week 48, as Assessed by Step Activity Monitoring (SAM) Change at Week 48	0.87 minutes Standard Deviation 57.833	-22.23 minutes Standard Deviation 84.759	-19.91 minutes Standard Deviation 91.960

SECONDARY outcome

Timeframe: Baseline, Week 48

The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean total step count/day/visit during the active periods was computed for each participant. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as the first time after 3:00 AM that \>2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was \<50% of the mean active period across all days for that participant's visit.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 48, as Assessed by SAM Baseline	5302.31 steps/day Standard Deviation 1907.058	4870.13 steps/day Standard Deviation 2165.522	5602.31 steps/day Standard Deviation 2023.543
Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 48, as Assessed by SAM Change at Week 48	-615.14 steps/day Standard Deviation 1468.452	-676.46 steps/day Standard Deviation 1717.535	-908.34 steps/day Standard Deviation 1999.969

SECONDARY outcome

Timeframe: Baseline, Week 48

The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean total step count/hour during the active periods for the days in a visit was computed for each participant. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as the first time after 3:00 AM that \>2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was \<50% of the mean active period across all days for that participant's visit.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 48, as Assessed by SAM Baseline	423.67 steps/hour Standard Deviation 168.754	383.62 steps/hour Standard Deviation 161.911	446.37 steps/hour Standard Deviation 160.666
Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 48, as Assessed by SAM Change at Week 48	-44.51 steps/hour Standard Deviation 125.154	-42.23 steps/hour Standard Deviation 126.429	-59.62 steps/hour Standard Deviation 153.054

SECONDARY outcome

Timeframe: Baseline, Week 48

SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). The maximum continuous 10-minute, 20-minute, 30-minute, and 60-minute total step counts were computed for each participant. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as the first time after 3:00 AM that \>2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was \<50% of the mean active period across all days for that participant's visit.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM Baseline: 10-minute total step count	35.77 steps Standard Deviation 10.222	32.24 steps Standard Deviation 11.374	36.76 steps Standard Deviation 8.935
Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM Change at Week 48: 10-minute total step count	-2.77 steps Standard Deviation 8.569	-2.79 steps Standard Deviation 6.355	-3.97 steps Standard Deviation 9.720
Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM Baseline: 20-minute total step count	29.13 steps Standard Deviation 9.272	25.68 steps Standard Deviation 10.038	29.74 steps Standard Deviation 8.205
Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM Change at Week 48: 20-minute total step count	-2.49 steps Standard Deviation 7.407	-2.40 steps Standard Deviation 5.806	-3.55 steps Standard Deviation 8.677
Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM Baseline: 30-minute total step count	25.00 steps Standard Deviation 8.053	22.08 steps Standard Deviation 9.206	25.70 steps Standard Deviation 7.350
Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM Change at Week 48: 30-minute total step count	-2.08 steps Standard Deviation 6.519	-2.31 steps Standard Deviation 5.505	-3.03 steps Standard Deviation 7.604
Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM Baseline: 60-minute total step count	18.58 steps Standard Deviation 6.210	16.52 steps Standard Deviation 7.199	19.50 steps Standard Deviation 5.887
Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, as Assessed by SAM Change at Week 48: 60-minute total step count	-1.50 steps Standard Deviation 5.177	-1.85 steps Standard Deviation 4.616	-2.33 steps Standard Deviation 6.241

SECONDARY outcome

Timeframe: Baseline, Week 48

SAM is a pedometer(worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again. Proportion of time during active periods spent at low activity(≤15 steps/minute), medium activity(16-30 steps/minute), and high activity(\>30 steps/minute) were computed for each participant. Mean obtained during Screening and following Week 1 visit were used as baseline data for analysis. For each day, an active period was defined as first time after 3:00 AM that \>2 strides/minute were recorded to the last time prior to midnight that \>2 strides/minute were recorded. Days were deleted on which such an active period was \<50% of the mean active period across all days for that participant's visit.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 Baseline: Time spent at low activity	32.91 percentage of time Standard Deviation 7.842	32.38 percentage of time Standard Deviation 8.213	32.86 percentage of time Standard Deviation 6.239
Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 Change at Week 48: Time spent at low activity	-2.06 percentage of time Standard Deviation 7.903	-1.12 percentage of time Standard Deviation 8.220	-1.11 percentage of time Standard Deviation 5.586
Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 Baseline: Time spent at medium activity	11.11 percentage of time Standard Deviation 4.013	10.00 percentage of time Standard Deviation 3.656	11.84 percentage of time Standard Deviation 4.304
Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 Change at Week 48: Time spent at medium activity	-1.35 percentage of time Standard Deviation 3.348	-0.69 percentage of time Standard Deviation 3.828	-1.92 percentage of time Standard Deviation 4.178
Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 Baseline: Time spent at high activity	6.59 percentage of time Standard Deviation 4.077	5.78 percentage of time Standard Deviation 3.785	7.17 percentage of time Standard Deviation 3.700
Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 Change at Week 48: Time spent at high activity	-0.66 percentage of time Standard Deviation 2.790	-0.96 percentage of time Standard Deviation 2.828	-1.03 percentage of time Standard Deviation 3.783

SECONDARY outcome

Timeframe: Baseline, Week 48

HRQL was measured via the PedsQL. The generic core module (including physical, emotional, social and school functioning scales) comprises 23 questions and the fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. The PedsQL was completed by both the participant and/or a parent/caregiver. Examples of items in each of the generic core module scales include: "It is hard for me to run"; "I feel sad or blue"; "I cannot do things that other kids my age can do;" and "It is hard to pay attention in class." Each of the generic core module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating better health-related quality of life. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Baseline: Physical functioning score	63.63 units on a scale Standard Deviation 20.029	59.27 units on a scale Standard Deviation 22.782	61.87 units on a scale Standard Deviation 19.411
Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Change at Week 48: Physical functioning score	-0.94 units on a scale Standard Deviation 19.125	2.37 units on a scale Standard Deviation 25.105	-1.00 units on a scale Standard Deviation 24.022
Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Baseline: Emotional functioning score	73.92 units on a scale Standard Deviation 20.418	73.70 units on a scale Standard Deviation 20.223	70.13 units on a scale Standard Deviation 19.332
Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Change at Week 48: Emotional functioning score	2.36 units on a scale Standard Deviation 16.742	-1.83 units on a scale Standard Deviation 23.725	4.30 units on a scale Standard Deviation 22.315
Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Baseline: Social functioning score	67.50 units on a scale Standard Deviation 21.749	65.09 units on a scale Standard Deviation 18.421	63.36 units on a scale Standard Deviation 20.476
Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Change at Week 48: Social functioning score	5.37 units on a scale Standard Deviation 20.463	3.89 units on a scale Standard Deviation 21.841	7.75 units on a scale Standard Deviation 18.870
Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Baseline: School functioning score	67.72 units on a scale Standard Deviation 19.276	64.55 units on a scale Standard Deviation 20.396	64.65 units on a scale Standard Deviation 17.841
Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Change at Week 48: School functioning score	3.61 units on a scale Standard Deviation 13.008	6.11 units on a scale Standard Deviation 23.765	4.06 units on a scale Standard Deviation 23.244

SECONDARY outcome

Timeframe: Baseline, Week 48

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Baseline: Physical functioning score	56.15 units on a scale Standard Deviation 19.955	54.96 units on a scale Standard Deviation 20.592	51.47 units on a scale Standard Deviation 19.274
Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Change at Week 48: Physical functioning score	0.03 units on a scale Standard Deviation 17.088	-3.10 units on a scale Standard Deviation 16.550	0.23 units on a scale Standard Deviation 23.712
Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Baseline: Emotional functioning score	70.08 units on a scale Standard Deviation 16.836	69.11 units on a scale Standard Deviation 18.711	65.96 units on a scale Standard Deviation 17.964
Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Change at Week 48: Emotional functioning score	4.07 units on a scale Standard Deviation 15.382	3.39 units on a scale Standard Deviation 18.068	1.21 units on a scale Standard Deviation 17.794
Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Baseline: Social functioning score	61.58 units on a scale Standard Deviation 15.825	62.77 units on a scale Standard Deviation 16.540	55.79 units on a scale Standard Deviation 18.269
Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Change at Week 48: Social functioning score	-0.40 units on a scale Standard Deviation 18.470	-1.09 units on a scale Standard Deviation 14.268	3.71 units on a scale Standard Deviation 14.130
Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Baseline: School functioning score	66.17 units on a scale Standard Deviation 18.258	66.16 units on a scale Standard Deviation 16.320	61.93 units on a scale Standard Deviation 13.587
Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 Change at Week 48: School functioning score	2.73 units on a scale Standard Deviation 18.490	-2.32 units on a scale Standard Deviation 15.462	3.48 units on a scale Standard Deviation 13.913

SECONDARY outcome

Timeframe: Baseline, Week 48

HRQL was measured via the PedsQL. The fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. PedsQL was completed by both the participant and/or a parent/caregiver. Fatigue-specific module obtains information relating to items such as: "I feel too tired to do things that I like to do"; "I spend a lot of time in bed"; and "I have trouble remembering more than one thing at a time;" Each of the fatigue-specific module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating less fatigue. Total score was the sum of all items over the number of items answered on all scales. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 Baseline	69.47 units on a scale Standard Deviation 16.525	71.62 units on a scale Standard Deviation 16.474	69.70 units on a scale Standard Deviation 15.263
Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 Change at Week 48	6.95 units on a scale Standard Deviation 13.460	0.45 units on a scale Standard Deviation 23.068	3.92 units on a scale Standard Deviation 16.512

SECONDARY outcome

Timeframe: Baseline, Week 48

HRQL was measured via the PedsQL. The fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. The PedsQL was completed by both the participant and/or a parent/caregiver. Fatigue-specific module obtains information relating to items such as: "I feel too tired to do things that I like to do"; "I spend a lot of time in bed"; and "I have trouble remembering more than one thing at a time;" Each of the fatigue-specific module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating less fatigue. Total score was the sum of all items over the number of items answered on all scales. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 Baseline	73.39 units on a scale Standard Deviation 13.671	70.71 units on a scale Standard Deviation 12.720	68.27 units on a scale Standard Deviation 13.170
Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 Change at Week 48	1.97 units on a scale Standard Deviation 13.873	1.27 units on a scale Standard Deviation 12.095	2.51 units on a scale Standard Deviation 12.039

SECONDARY outcome

Timeframe: Week 48

TSQM consisted of 14 questions about treatment satisfaction with drug in 4 domains: Effectiveness (Questions 1-3 scored as 1 \[extremely dissatisfied\] to 7 \[extremely satisfied\]), Side Effects (question 4 scored as 0 \[no\] or 1 \[yes\]; question 5 scored as 1 \[extremely bothersome\] to 5 \[not at all bothersome\]; questions 6 - 8 scored as 1 \[a great deal\] to 5 \[not at all\]), Convenience (questions 9 and 10 scored as 1 \[extremely difficult\] to 7 \[extremely easy\]; question 11 scored as 1 \[extremely inconvenient\] to 5 \[extremely convenient\]) and Global Satisfaction (question 12 scored as 1 \[not at all confident\] to 7 \[extremely confident\]; question 13 scored as 1 \[not at all certain\] to 5 \[extremely certain\]; question 14 scored as 1 \[extremely dissatisfied\] to 5 \[extremely satisfied\]). The scores of each of the domains were added together and an algorithm was used to create a score of 0 to 100, with higher scores indicating better treatment satisfaction.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score Effectiveness score	55.97 units on a scale Standard Deviation 27.796	54.60 units on a scale Standard Deviation 22.307	51.26 units on a scale Standard Deviation 23.536
Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score Side-effects score	96.36 units on a scale Standard Deviation 11.199	97.77 units on a scale Standard Deviation 7.578	96.89 units on a scale Standard Deviation 8.874
Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score Convenience score	55.85 units on a scale Standard Deviation 17.008	58.23 units on a scale Standard Deviation 19.040	60.91 units on a scale Standard Deviation 16.665
Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score Global satisfaction score	61.04 units on a scale Standard Deviation 25.967	61.19 units on a scale Standard Deviation 23.691	57.56 units on a scale Standard Deviation 21.851

SECONDARY outcome

Timeframe: Baseline, Week 48

Number of falls was determined by daily diary records maintained by participants and/or parent/caregivers.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Participant/Caregiver-Reported Number of Daily Accidental Falls at Week 48 Baseline	0.40 falls/day Standard Deviation 0.597	0.27 falls/day Standard Deviation 0.480	0.54 falls/day Standard Deviation 0.943
Change From Baseline in Participant/Caregiver-Reported Number of Daily Accidental Falls at Week 48 Change at Week 48	-0.10 falls/day Standard Deviation 0.466	-0.06 falls/day Standard Deviation 0.501	0.20 falls/day Standard Deviation 1.282

SECONDARY outcome

Timeframe: Baseline, Week 48

Basic attention and working memory was measured using the digit span task. A series of digits (0-9) were presented to the child in an auditory format only. The task had 2 parts; in the forward condition, the child was requested to repeat back the digits in the order they were presented and in the backward condition, he was requested to reverse the order of presentation. A raw score of the total number of correct responses was converted to an age-scaled-score (z-score) by subtracting the corresponding mean and dividing by the corresponding standard deviation of a reference population for that age.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 Baseline: Forward condition	3.59 z-score Standard Deviation 2.554	2.89 z-score Standard Deviation 2.180	2.84 z-score Standard Deviation 1.675
Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 Change at Week 48: Forward condition	0.39 z-score Standard Deviation 1.677	0.50 z-score Standard Deviation 1.767	0.40 z-score Standard Deviation 1.550
Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 Baseline: Backward condition	1.73 z-score Standard Deviation 1.846	1.70 z-score Standard Deviation 1.868	1.59 z-score Standard Deviation 1.460
Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 Change at Week 48: Backward condition	0.56 z-score Standard Deviation 1.500	0.33 z-score Standard Deviation 1.441	0.59 z-score Standard Deviation 1.203

SECONDARY outcome

Timeframe: Baseline, Week 48

The heart rate was measured with a Polar RS400 heart rate monitor, which consists of a transmitter strap worn around the chest and a wristwatch receiver. The monitor produces a digital text file with 1 value per minute that represents the mean heart rate for that minute. Mean heart rates values were collected prior to, during, and after the 6MWT. The participant rested for 5 minutes in a sitting position prior to the 6MWT, and the mean heart rate for the last minute of this rest period was collected and documented as the resting heart rate. During the 6MWT, the mean heart rate was collected and documented as the active heart rate. After completing the 6MWT and resting for 3 minutes, the mean heart rate for 1 minute was collected and documented as the recovery heart rate.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 Baseline: Resting heart rate	105.47 beats/minute Standard Deviation 12.908	109.70 beats/minute Standard Deviation 9.908	104.07 beats/minute Standard Deviation 11.588
Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 Change at Week 48: Resting heart rate	-0.63 beats/minute Standard Deviation 13.008	-0.36 beats/minute Standard Deviation 10.223	-0.26 beats/minute Standard Deviation 15.614
Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 Baseline: Active heart rate	142.67 beats/minute Standard Deviation 18.070	141.77 beats/minute Standard Deviation 15.574	136.67 beats/minute Standard Deviation 20.713
Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 Change at Week 48: Active heart rate	-5.00 beats/minute Standard Deviation 21.976	2.39 beats/minute Standard Deviation 19.095	1.65 beats/minute Standard Deviation 21.295
Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 Baseline: Recovery heart rate	109.90 beats/minute Standard Deviation 12.633	113.48 beats/minute Standard Deviation 10.340	107.86 beats/minute Standard Deviation 12.066
Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 Change at Week 48: Recovery heart rate	-0.23 beats/minute Standard Deviation 13.475	-1.33 beats/minute Standard Deviation 13.270	0.54 beats/minute Standard Deviation 15.181

SECONDARY outcome

Timeframe: Baseline, Week 48

Blood samples collected for chemistry assays were used to quantify serum CK concentrations. Serum CK was assessed as a potential biomarker for muscle fragility, with a reduction in serum CK considered to be a positive outcome.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 48 Baseline	10853.65 units/liter (U/L) Standard Deviation 6251.136	12084.70 units/liter (U/L) Standard Deviation 7772.631	10569.60 units/liter (U/L) Standard Deviation 6488.477
Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 48 Change at Week 48	-1680.09 units/liter (U/L) Standard Deviation 4264.769	-2146.32 units/liter (U/L) Standard Deviation 7151.944	-1235.13 units/liter (U/L) Standard Deviation 4323.943

SECONDARY outcome

Timeframe: Pre-Treatment (1 week prior to baseline), post-treatment (Week 36)

Population: As-treated population included all randomized participants who actually received any study treatment. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoint.

Immunofluorescence evidence of a change in dystrophin expression on biceps muscle biopsy was defined as an increase in the staining of the sarcolemmal membrane with an antibody to the C-terminal portion of the dystrophin protein (excluding revertant fibers) between the pre-treatment (1 week prior to Baseline visit) and post-treatment (Week 36) biopsies. The biceps muscle was biopsied from one arm for confirmation of the absence or reduced levels of dystrophin prior to treatment initiation and from the other arm to assess for production of dystrophin post-treatment.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Percent Change From Pre-Treatment Visit (1 Week Prior to Baseline Visit) in Biceps Muscle Dystrophin Expression at Post-Treatment Visit (Week 36), as Determined by Immunofluorescence Pre-treatment	336.096 percent change Standard Deviation 138.9753	359.797 percent change Standard Deviation 142.7361	357.271 percent change Standard Deviation 139.6650
Percent Change From Pre-Treatment Visit (1 Week Prior to Baseline Visit) in Biceps Muscle Dystrophin Expression at Post-Treatment Visit (Week 36), as Determined by Immunofluorescence Percent change post-treatment	-1.278 percent change Standard Deviation 27.7432	-2.128 percent change Standard Deviation 28.8287	-0.898 percent change Standard Deviation 19.2112

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 54

Population: As-treated population included all randomized participants who actually received any study treatment.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. Treatment-emergent adverse event (TEAE) was defined as an adverse event that occurred or worsened in the period extending from first dose of study drug to 6 weeks after the last dose of study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Percentage of Participants With Treatment-Emergent Adverse Events (AEs)	95.0 percentage of participants	96.5 percentage of participants	98.2 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 48

Population: As-treated population included all randomized participants who actually received any study treatment.

Study drug compliance was assessed by participant daily diary and quantification of used and unused study drug. Compliance was assessed in terms of the percentage of drug actually taken relative to the amount that should have been taken during the study.

Outcome measures

Outcome measures
Measure	High-Dose Ataluren n=60 Participants Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 Participants Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Study Drug Compliance	97.87 percentage of drug Interval 34.9 to 99.6	97.03 percentage of drug Interval 64.5 to 99.8	97.74 percentage of drug Interval 76.6 to 99.9

Adverse Events

High-Dose Ataluren

Serious events: 2 serious events

Other events: 58 other events

Deaths: 0 deaths

Low-Dose Ataluren

Serious events: 2 serious events

Other events: 56 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	High-Dose Ataluren n=60 participants at risk Participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for 48 weeks.	Low-Dose Ataluren n=57 participants at risk Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.	Placebo n=57 participants at risk Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.
Cardiac disorders Supraventricular tachycardia	1.7% 1/60 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	0.00% 0/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	0.00% 0/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/60 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	0.00% 0/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	1.8% 1/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.
Infections and infestations Appendicitis	0.00% 0/60 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	1.8% 1/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	0.00% 0/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.
Infections and infestations Influenza	0.00% 0/60 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	0.00% 0/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	1.8% 1/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.
Infections and infestations Varicella	0.00% 0/60 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	0.00% 0/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	1.8% 1/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/60 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	0.00% 0/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	1.8% 1/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.
Injury, poisoning and procedural complications Lower limb fracture	1.7% 1/60 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	0.00% 0/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	0.00% 0/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/60 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	1.8% 1/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	0.00% 0/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.
Nervous system disorders Grand mal convulsion	0.00% 0/60 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	0.00% 0/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.	1.8% 1/57 • Baseline up to 6 weeks after the last dose of study drug (Week 54) As-treated population included all randomized participants who actually received any study treatment.

Other adverse events

Additional Information

Patient Advocacy

PTC Therapeutics, Inc.

Phone: 1-866-562-4620

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER