Trial Outcomes & Findings for Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD) (NCT NCT01826487)

Last Updated: 2020-08-04

Results Overview

The 6MWD test is a non-encouraged test performed in a 30 meters long flat corridor, where the participant is 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. Participants with confirmed loss of ambulation at a particular visit were assigned a 6MWD result of 0. Baseline and Week 48 6MWD values are each the average of two valid 6MWD values, or a single available value if one was missing.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

230 participants

Primary outcome timeframe

Baseline, Week 48

Results posted on

2020-08-04

Participant Flow

A total of 291 participants were screened for eligibility, of which 61 participants did not meet entry criteria.

A total of 230 eligible participants were randomized in 1:1 ratio to receive either placebo or ataluren. 2 participants, 1 in each treatment arm, were excluded from intent-to-treat (ITT) population; as they did not have at least 1 valid post-baseline 6-minute walk distance (6MWD) value, a requirement for inclusion in ITT population.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo matched to ataluren orally 3 times a day (TID) at morning, midday, and evening for 48 weeks.	Ataluren Participants received ataluren suspension orally TID, 10 milligrams/kilogram (mg/kg) at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
Overall Study STARTED	115	115
Overall Study As-treated Population	115	115
Overall Study ITT Population	114	114
Overall Study COMPLETED	111	110
Overall Study NOT COMPLETED	4	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo matched to ataluren orally 3 times a day (TID) at morning, midday, and evening for 48 weeks.	Ataluren Participants received ataluren suspension orally TID, 10 milligrams/kilogram (mg/kg) at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks.
Overall Study Adverse Event	1	1
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	1	3
Overall Study Protocol Violation	1	1

Baseline Characteristics

'Number analyzed' signifies participants of as-treated population analyzed for this parameter.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=115 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Ataluren n=115 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.	Total n=230 Participants Total of all reporting groups
Age, Continuous	9.0 years STANDARD_DEVIATION 1.65 • n=115 Participants	8.9 years STANDARD_DEVIATION 1.79 • n=115 Participants	8.9 years STANDARD_DEVIATION 1.72 • n=230 Participants
Sex: Female, Male Female	0 Participants n=115 Participants	0 Participants n=115 Participants	0 Participants n=230 Participants
Sex: Female, Male Male	115 Participants n=115 Participants	115 Participants n=115 Participants	230 Participants n=230 Participants
6 Minute Walk Distance (6MWD)	362.69 meters STANDARD_DEVIATION 81.424 • n=115 Participants	364.04 meters STANDARD_DEVIATION 73.342 • n=115 Participants	363.36 meters STANDARD_DEVIATION 77.322 • n=230 Participants
Time to Walk/Run 10 Meters	6.83 seconds STANDARD_DEVIATION 2.924 • n=115 Participants	6.66 seconds STANDARD_DEVIATION 3.078 • n=115 Participants	6.75 seconds STANDARD_DEVIATION 2.996 • n=230 Participants
Time to Climb 4 Stairs	6.76 seconds STANDARD_DEVIATION 7.287 • n=112 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.	5.99 seconds STANDARD_DEVIATION 5.347 • n=112 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.	6.38 seconds STANDARD_DEVIATION 6.389 • n=224 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
Time to Descend 4 Stairs	5.05 seconds STANDARD_DEVIATION 5.362 • n=109 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.	5.07 seconds STANDARD_DEVIATION 5.157 • n=112 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.	5.06 seconds STANDARD_DEVIATION 5.247 • n=221 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
Physical Function Total Score as Measured by North Star Ambulatory Assessment (NSAA)	60.2 units on a scale STANDARD_DEVIATION 18.37 • n=114 Participants • 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.	60.9 units on a scale STANDARD_DEVIATION 17.97 • n=114 Participants • 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.	60.6 units on a scale STANDARD_DEVIATION 18.14 • n=228 Participants • 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.
Baseline 6MWT <300 meters	22 Participants n=115 Participants	25 Participants n=115 Participants	47 Participants n=230 Participants
Baseline 6MWT >=300 to <400 meters	52 Participants n=115 Participants	47 Participants n=115 Participants	99 Participants n=230 Participants
Baseline 6MWT >=400 meters	41 Participants n=115 Participants	43 Participants n=115 Participants	84 Participants n=230 Participants
Pediatric Outcomes Data Collection Instrument (PODCI) Scores Transfers/Basic Mobility Score	81.4 units on a scale STANDARD_DEVIATION 15.79 • n=114 Participants • 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.	83.9 units on a scale STANDARD_DEVIATION 13.10 • n=114 Participants • 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.	82.7 units on a scale STANDARD_DEVIATION 14.53 • n=228 Participants • 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.
Pediatric Outcomes Data Collection Instrument (PODCI) Scores Sports/Physical Functioning Score	56.0 units on a scale STANDARD_DEVIATION 20.94 • n=114 Participants • 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.	56.2 units on a scale STANDARD_DEVIATION 18.94 • n=114 Participants • 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.	56.1 units on a scale STANDARD_DEVIATION 19.92 • n=228 Participants • 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.

PRIMARY 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. Multiple imputation was applied to impute missing values within the treatment groups.

Outcome measures

Outcome measures
Measure	Placebo n=114 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Ataluren n=114 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.
Change From Baseline in 6MWD at Week 48	-60.67 meters Standard Error 9.323	-47.69 meters Standard Error 9.247

SECONDARY outcome

Timeframe: Baseline to Week 48

The 6MWD test is a non-encouraged test performed in a 30 meters long flat corridor, where the participant is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures by measuring the 6MWD in meters. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test. Time to 10% persistent worsening in 6MWD was defined as the last time that 6MWD was not 10% worse compared with baseline. Time to 10% persistent worsening in 6MWD \<300 meters, \>=300 to 400 meters, and \>=400 meters was evaluated. For participants who did not have 10% 6MWD worsening or who were removed from study, time to 10% 6MWD worsening was censored at the time of the last 6MWD test. Participants who became non-ambulatory were considered to have 10% worsening.

Outcome measures

Outcome measures
Measure	Placebo n=114 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Ataluren n=114 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.
Time to 10 Percent (%) Persistent Worsening in 6MWD <300 meters	56 days Interval 1.0 to 111.0	164 days Interval 1.0 to 225.0
Time to 10 Percent (%) Persistent Worsening in 6MWD >=300 to <400 meters	280 days Interval 169.0 to Due to smaller number of participants with an event, upper limit of 95% confidence interval (CI) could not be calculated.	NA days Interval 280.0 to Due to smaller number of participants with an event, median and upper limit of 95% CI could not be calculated.
Time to 10 Percent (%) Persistent Worsening in 6MWD >=400 meters	NA days Due to smaller number of participants with an event, median and 95% CI could not be calculated.	NA days Due to smaller number of participants with an event, median and 95% CI could not be calculated.

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, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

During the test for walking/running 10 meters, the method of walk/run used by the participant was categorized as follows: 1. Unable to walk independently; 2. Unable to walk independently but can walk with support from a person or with assistive device (full leg calipers \[knee-ankle-foot orthoses \] or walker); 3. Highly adapted gait, 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). If the time taken to perform a test exceeded 30 seconds or if a participant could not perform the test due to disease progression, a value of 30 seconds was used. A cumulative change from baseline data has been reported.

Outcome measures

Outcome measures
Measure	Placebo n=110 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Ataluren n=109 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.
Change From Baseline in Time to Walk/Run 10 Meters at Week 48	3.47 seconds Standard Deviation 6.393	2.27 seconds Standard Deviation 5.216

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, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

During the test for stair-climbing, the method of climbing used by the participant was categorized as follows: 1. Unable to up climb 4 standard stairs; 2. Climbs 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), using both arms on one or both handrails; 3. Climbs 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), using one arm on one handrail; 4. Climbs 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), 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. A cumulative change from baseline data has been reported.

Outcome measures

Outcome measures
Measure	Placebo n=103 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Ataluren n=105 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.
Change From Baseline in Time to Climb 4 Stairs at Week 48	4.46 seconds Standard Deviation 7.310	2.65 seconds Standard Deviation 5.297

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, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

During the test for stair-descending, the method of descending used by the participant was categorized as follows: 1. Unable to descend 4 standard stairs; 2. Descends 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), using both arms on one or both handrails; 3. Descends 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), using one arm on one handrail; 4. Descends 4 standard stairs "marking time" (climbs one foot at a time, with both feet on a step before moving to next step), not needing handrail; 5. Descends 4 standard stairs alternating feet, needs handrail for support; 6. Descends 4 standard stairs alternating feet, not needing handrail support. A cumulative change from baseline data has been reported.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Ataluren n=106 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.
Change From Baseline in Time to Descend 4 Stairs at Week 48	3.97 seconds Standard Deviation 7.854	2.15 seconds Standard Deviation 5.306

SECONDARY 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	Placebo n=115 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Ataluren n=115 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.
Percentage of Participants With Treatment-Emergent Adverse Events (AEs)	87.8 percentage of participants	89.6 percentage of participants

OTHER_PRE_SPECIFIED 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, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Physical function was assessed via the NSAA, a functional scale specifically designed for ambulant Duchenne muscular dystrophy (DMD) participants. The assessment comprised tests for 17 abilities of a participant, such as ability to stand, rise from the floor, get from lying to sitting, get from sitting to standing, raise one's head, stand on one's heels, hop, jump, and run. For each activity, a score of 0, 1, or 2 was recorded, with 0 = "unable to achieve independently," 1 = "modified method but achieves goal independent of physical assistance from another," or 2 = "normal- achieves goal without any assistance." The sum of these scores (except for 'raise one's head' activity score) was reported as the ordinal total score, which was transformed to a linear total score ranging from 0 (worst) to 100 (best). Participants with confirmed loss of ambulation at a particular visit were assigned a score of 0.

Outcome measures

Outcome measures
Measure	Placebo n=108 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Ataluren n=106 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.
Change From Baseline in Physical Function Total Score as Measured by NSAA at Week 48	-8.4 units on a scale Standard Deviation 10.65	-6.3 units on a scale Standard Deviation 10.64

OTHER_PRE_SPECIFIED 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 for specified categories.

Changes in activities of daily living and disease symptoms were captured via a DMD-specific survey administered by Site personnel. At screening or baseline, the participant and/or parent/caregiver were asked to identify any activities of daily living (for example, ambulation, balance, personal hygiene/grooming, dressing and undressing, self-feeding, using the bathroom, handwriting, school performance, behavior or energy level) or symptoms that were affected by the participant's DMD. At post-baseline visit (Week 48), the same participant and/or parent/caregiver was asked to describe any changes from baseline in those activities of daily living/symptoms, within the following categories: physical functioning; general energy level; cognition/school function; emotional/social functioning; and sleep. Changes from baseline were reported on a 5-point Likert scale: 1 (much worse), 2 (slightly worse), 3 (unchanged), 4 (slightly better), or 5 (much better).

Outcome measures

Outcome measures
Measure	Placebo n=114 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Ataluren n=114 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.
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Other · Unchanged	38 Participants	44 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Other · Slightly worse	7 Participants	8 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Emotional/Social Functioning · Slightly worse	5 Participants	6 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Other · Slightly better	9 Participants	10 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Emotional/Social Functioning · Much worse	2 Participants	2 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel General Energy Level · Much better	3 Participants	8 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Upper Extremity Activity · Much better	1 Participants	4 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Upper Extremity Activity · Slightly better	7 Participants	7 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Upper Extremity Activity · Unchanged	67 Participants	73 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Upper Extremity Activity · Slightly worse	6 Participants	2 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Upper Extremity Activity · Much worse	1 Participants	2 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Walking · Much better	5 Participants	8 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Walking · Slightly better	13 Participants	16 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Walking · Unchanged	57 Participants	60 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Walking · Slightly worse	19 Participants	21 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Walking · Much worse	18 Participants	3 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Climbing Stairs · Much better	4 Participants	4 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Climbing Stairs · Slightly better	8 Participants	13 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Climbing Stairs · Unchanged	61 Participants	65 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Climbing Stairs · Slightly worse	17 Participants	15 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Climbing Stairs · Much worse	15 Participants	13 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Other · Much better	4 Participants	5 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel General Energy Level · Slightly better	12 Participants	12 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel General Energy Level · Unchanged	54 Participants	63 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel General Energy Level · Slightly worse	11 Participants	5 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel General Energy Level · Much worse	3 Participants	1 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Sleep · Much better	3 Participants	3 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Sleep · Slightly better	4 Participants	8 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Sleep · Unchanged	73 Participants	76 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Sleep · Slightly worse	5 Participants	2 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Sleep · Much worse	0 Participants	2 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Other · Much better	0 Participants	1 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Other · Slightly better	5 Participants	6 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Other · Unchanged	15 Participants	13 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Other · Slightly worse	2 Participants	3 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Other · Much worse	1 Participants	0 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Other · Much worse	7 Participants	1 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Cognition/Social Functioning · Much better	6 Participants	5 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Cognition/Social Functioning · Slightly better	12 Participants	20 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Cognition/Social Functioning · Unchanged	71 Participants	74 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Cognition/Social Functioning · Slightly worse	3 Participants	3 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Cognition/Social Functioning · Much worse	0 Participants	2 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Emotional/Social Functioning · Much better	3 Participants	8 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Emotional/Social Functioning · Slightly better	9 Participants	21 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 48, as Assessed by a Standardized Survey Administered by Site Personnel Emotional/Social Functioning · Unchanged	75 Participants	68 Participants

OTHER_PRE_SPECIFIED 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, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Changes in health-related quality of life (HRQL) were measured via the PODCI questionnaire that has been shown to correlate with disease progression and clinical outcome measures in DMD. PODCI includes a Global Functioning Scale and 5 core scales: Upper Extremity and Physical Function,Transfer/Basic Mobility, Sports/Physical Functioning, Pain/Comfort,and Happiness. The following PODCI domains were prespecified in the protocol for analysis:Transfers/Basic Mobility domain assesses difficulty experienced in performing routine motor activities in daily life. Sports/Physical Functioning domain assesses difficulty encountered in participating in more active recreational activities. Each domain was scored from 0 to 100, with 0 representing a poor outcome/worse health, while 100 representing the highest level of functioning and least pain.

Outcome measures

Outcome measures
Measure	Placebo n=110 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Ataluren n=109 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.
Change From Baseline in PODCI Transfers/Basic Mobility and Sports/Physical Functioning Scores at Week 48 Transfers/Basic Mobility Score	-8.8 units on a scale Standard Deviation 15.80	-6.6 units on a scale Standard Deviation 14.76
Change From Baseline in PODCI Transfers/Basic Mobility and Sports/Physical Functioning Scores at Week 48 Sports/Physical Functioning Score	-7.3 units on a scale Standard Deviation 15.87	-5.6 units on a scale Standard Deviation 15.91

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 8, 16, 24, 32, 40, and 48

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

Plasma samples for the determination of ataluren concentrations were analyzed using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC/MS-MS) method with a lower limit of quantitation of 0.5 micrograms/milliliter (mcg/mL).

Outcome measures

Outcome measures
Measure	Placebo n=115 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	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.
Ataluren Plasma Concentration Week 08	4.230 mcg/mL Standard Deviation 5.3913	—
Ataluren Plasma Concentration Week 16	3.429 mcg/mL Standard Deviation 3.9275	—
Ataluren Plasma Concentration Week 24	3.323 mcg/mL Standard Deviation 3.6135	—
Ataluren Plasma Concentration Week 32	3.480 mcg/mL Standard Deviation 3.1053	—
Ataluren Plasma Concentration Week 40	3.997 mcg/mL Standard Deviation 4.7615	—
Ataluren Plasma Concentration Week 48	3.544 mcg/mL Standard Deviation 3.8082	—

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 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	Placebo n=115 Participants Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Ataluren n=115 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.
Study Drug Compliance	95.1 percentage of drug Standard Deviation 9.43	95.7 percentage of drug Standard Deviation 7.57

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 99 other events

Deaths: 0 deaths

Ataluren

Serious events: 4 serious events

Other events: 103 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=115 participants at risk Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks.	Ataluren n=115 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.
Musculoskeletal and connective tissue disorders Tendon disorder	0.87% 1/115 • Number of events 1 • 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% 0/115 • 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 Post-traumatic pain	0.87% 1/115 • Number of events 1 • 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% 0/115 • 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 Pneumonia	1.7% 2/115 • Number of events 2 • 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% 0/115 • 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 Bronchiolitis	0.87% 1/115 • Number of events 1 • 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% 0/115 • 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.
Respiratory, thoracic and mediastinal disorders Adenoidal hypertrophy	0.87% 1/115 • Number of events 1 • 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% 0/115 • 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.
Respiratory, thoracic and mediastinal disorders Nasal turbinate hypertrophy	0.87% 1/115 • Number of events 1 • 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% 0/115 • 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.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/115 • 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.	0.87% 1/115 • Number of events 1 • 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.
Cardiac disorders Myocarditis	0.00% 0/115 • 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.	0.87% 1/115 • Number of events 1 • 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 Gastroenteritis	0.00% 0/115 • 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.	0.87% 1/115 • Number of events 1 • 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% 0/115 • 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.	0.87% 1/115 • Number of events 1 • 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	0.00% 0/115 • 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.	0.87% 1/115 • Number of events 1 • 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