Trial Outcomes & Findings for An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy (NCT NCT02090959)

NCT ID: NCT02090959

Last Updated: 2020-08-11

Results Overview

An adverse event (AE): any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of AEs: graded per Common Terminology Criteria for AEs (CTCAE), Version 3.0 as Grade 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). Drug-related AEs: AEs with possible, probable, unlikely relationship, or unrelated to study drug. Serious AEs (SAEs): death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention. TEAE: an AE that occurred or worsened in the period extending from first dose of study drug in this study to 6 weeks after last dose of study drug in this study. A summary of other non-serious AEs and all SAEs, regardless of causality is located in Reported AE section.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

219 participants

Primary outcome timeframe

Baseline (Day 1) up to 6 weeks post-treatment (Week 150)

Results posted on

2020-08-11

Participant Flow

All participants who successfully completed the double-blind, placebo-controlled Phase 3 study (PTC124-GD-020-DMD \[NCT01826487\]) were screened for this open-label extension study.

A total of 221 participants completed the double-blind Phase 3 Study PTC124-GD-020-DMD. Of the 221 participants who completed Study PTC124-GD-020-DMD, 219 participants were enrolled in this open-label extension study and 218 were treated.

Participant milestones

Participant milestones
Measure	Ataluren Participants received ataluren suspension orally 3 times a day (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 up to 144 weeks.
Overall Study STARTED	219
Overall Study As-treated Population	218
Overall Study COMPLETED	68
Overall Study NOT COMPLETED	151

Reasons for withdrawal

Reasons for withdrawal
Measure	Ataluren Participants received ataluren suspension orally 3 times a day (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 up to 144 weeks.
Overall Study Withdrawal by Subject	10
Overall Study Adverse Event	1
Overall Study Investigator decision	2
Overall Study Study termination	6
Overall Study Enrolled but not treated	1
Overall Study Transfer for compassionate use medicine	4
Overall Study Move to medical need program	3
Overall Study Entered in to other study	34
Overall Study Switched to commercial supply	88
Overall Study Other than specified	2

Baseline Characteristics

This baseline characteristic was analyzed on ambulatory participants only.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ataluren n=218 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 up to 144 weeks.
Age, Continuous	9.9 years STANDARD_DEVIATION 1.78 • n=218 Participants
Sex: Female, Male Female	0 Participants n=218 Participants
Sex: Female, Male Male	218 Participants n=218 Participants
Race/Ethnicity, Customized White	169 Participants n=218 Participants
Race/Ethnicity, Customized Black	2 Participants n=218 Participants
Race/Ethnicity, Customized Asian	13 Participants n=218 Participants
Race/Ethnicity, Customized Hispanic	12 Participants n=218 Participants
Race/Ethnicity, Customized Other	8 Participants n=218 Participants
Race/Ethnicity, Customized Missing	14 Participants n=218 Participants
6 Minute Walk Distance (6MWD)	349.885 meters STANDARD_DEVIATION 105.7913 • n=198 Participants • This baseline characteristic was analyzed on ambulatory participants only.
Time to Stand From Supine Position	13.0 seconds STANDARD_DEVIATION 10.34 • n=199 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
Time to Walk/Run 10 Meters	9.31 seconds STANDARD_DEVIATION 7.388 • n=215 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
Time to Climb 4 Stairs	9.03 seconds STANDARD_DEVIATION 8.939 • n=203 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
Time to Descend 4 Stairs	7.52 seconds STANDARD_DEVIATION 8.401 • n=204 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
North Star Ambulatory Assessment (NSAA) Total Score	20.73 units on a scale STANDARD_DEVIATION 8.513 • n=195 Participants • This baseline parameter was analyzed on ambulatory participants with a baseline value.
Performance Upper Limb (PUL) Total Score	68.7 units on a scale STANDARD_DEVIATION 4.61 • n=210 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
Percent Predicted Forced Vital Capacity (FVC)	59.42 percent predicted FVC STANDARD_DEVIATION 13.843 • n=210 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)	53.76 percent predicted FEV1 STANDARD_DEVIATION 12.870 • n=209 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
Peak Expiratory Flow (PEF)	3.36 liters/second (L/sec) STANDARD_DEVIATION 1.055 • n=213 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
Peak Cough Flow (PCF)	3.30 L/sec STANDARD_DEVIATION 1.139 • n=194 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
Pediatric Outcomes Data Collection Instrument (PODCI) Transfers/Basic Mobility Score	74.6 units on a scale STANDARD_DEVIATION 23.66 • n=216 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
Blood Pressure Systolic blood pressure	106.3 millimeters of mercury (mm Hg) STANDARD_DEVIATION 10.72 • n=217 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
Blood Pressure Diastolic blood pressure	68.6 millimeters of mercury (mm Hg) STANDARD_DEVIATION 11.01 • n=217 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
Pulse Rate	97.0 beats/minute STANDARD_DEVIATION 13.31 • n=217 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.
Body Temperature	36.47 degrees centigrade STANDARD_DEVIATION 0.453 • n=217 Participants • 'Number analyzed' signifies participants of as-treated population analyzed for this parameter.

PRIMARY outcome

Timeframe: Baseline (Day 1) up to 6 weeks post-treatment (Week 150)

Population: AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.

Outcome measures

Outcome measures
Measure	Ataluren n=218 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 up to 144 weeks.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any AEs	202 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) SAEs	24 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Drug-Related AEs	44 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) AEs Leading to Withdrawal From Study	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Mild AEs	87 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Moderate AEs	71 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Severe AEs	42 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Life-threatening AEs	2 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) up to 6 weeks post-treatment (Week 150)

Population: AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.

Abnormalities in laboratory variables as pre-defined in protocol for safety-monitoring were: Hepatic (Serum alanine aminotransferase \[ALT\]: increase of greater than \[\>\] 150 units/liter \[U/L\] with stable or decrease of creatinine kinese \[CK\]; Serum glutamyl amino transferase \[GGT\] \[U/L\]: Grade 2 \[\>2.5 - 5.0 \* upper limit of normal {ULN}\]), renal (Serum cystatin C miiligrams/liter \[mg/L\] \>1.33 - 2.00 mg/L; Serum blood urea nitrogen \[UREAN\] \[millimoles/liter {mmol/L}\] greater than or equal to \[≥\]1.5 - 3.0 \* ULN; Urine occult blood: 2+ \[Small\], 3+ \[Moderate\], 4+ \[Large\]), and electrolytes (Serum sodium: low \[mmol/L\], Grade 3-4 \[less than {\<}130 mmol/L\]; serum potassium: high \[mmol/L\], Grade 3-4 \[\>6.0 mmol/L\]; and Serum bicarbonate \[mmol/L\]: Grade 2 \[\<16 - 11 mmol/L\]).

Outcome measures

Outcome measures
Measure	Ataluren n=218 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 up to 144 weeks.
Number of Participants With Abnormalities in Clinical Laboratory Parameters	29 Participants

SECONDARY outcome

Timeframe: Baseline, Week 144

Population: AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline 6MWD value at specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Ataluren n=26 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 up to 144 weeks.
Change From Baseline in 6MWD at Week 144	-98.18 meters Standard Deviation 86.604

SECONDARY outcome

Timeframe: Baseline, Week 144

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.

Outcome measures

Outcome measures
Measure	Ataluren n=19 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 up to 144 weeks.
Change From Baseline in Time to Stand From Supine Position at Week 144	5.22 seconds Standard Deviation 5.104

SECONDARY outcome

Timeframe: Baseline, Week 144

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.

Outcome measures

Outcome measures
Measure	Ataluren n=27 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 up to 144 weeks.
Change From Baseline in Time to Walk/Run 10 Meters at Week 144	2.29 seconds Standard Deviation 1.991

SECONDARY outcome

Timeframe: Baseline, Week 144

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.

Outcome measures

Outcome measures
Measure	Ataluren n=22 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 up to 144 weeks.
Change From Baseline in Time to Climb 4 Stairs at Week 144	4.01 seconds Standard Deviation 7.260

SECONDARY outcome

Timeframe: Baseline, Week 144

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.

Outcome measures

Outcome measures
Measure	Ataluren n=22 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 up to 144 weeks.
Change From Baseline in Time to Descend 4 Stairs at Week 144	2.45 seconds Standard Deviation 5.853

SECONDARY outcome

Timeframe: Baseline, Week 144

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	Ataluren n=40 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 up to 144 weeks.
Change From Baseline in Physical Function Total Score as Measured by NSAA at Week 144	-7.95 units on a scale Standard Deviation 5.611

SECONDARY outcome

Timeframe: Baseline, Week 144

The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into shoulder level (4 items), elbow level (9 items), and distal level (8 items) dimensions. Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. Each dimension was scored separately with a maximum score of 16 for shoulder level, 34 for elbow level, and 24 for distal level. Total score was calculated by adding the 3 level scores, with a maximum global score of 74 (total score range = 0-74). Higher score = better outcome.

Outcome measures

Outcome measures
Measure	Ataluren n=44 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 up to 144 weeks.
Change From Baseline in PUL Total Score at Week 144	-4.0 units on a scale Standard Deviation 7.49

SECONDARY outcome

Timeframe: Baseline, Week 144

FVC is a standard pulmonary function test. FVC was defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Percent predicted FVC (in %) = \[(observed FVC)/(predicted FVC)\]\*100.

Outcome measures

Outcome measures
Measure	Ataluren n=63 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 up to 144 weeks.
Change From Baseline in Percent Predicted FVC as Measured by Spirometry at Week 144	3.51 percent predicted FVC Standard Deviation 14.253

SECONDARY outcome

Timeframe: Baseline, Week 144

FEV1 is a standard pulmonary function test. FEV1 was defined as the volume of air that can forcibly be blown out in 1 second, after full inspiration in the upright position, measured in liters. Percent predicted FEV1 (in %) = \[(observed FEV1)/(predicted FEV1)\]\*100.

Outcome measures

Outcome measures
Measure	Ataluren n=63 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 up to 144 weeks.
Change From Baseline in Percent Predicted FEV1 as Measured by Spirometry at Week 144	1.40 percent predicted FEV1 Standard Deviation 15.319

SECONDARY outcome

Timeframe: Baseline, Week 144

PEF was defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated.

Outcome measures

Outcome measures
Measure	Ataluren n=65 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 up to 144 weeks.
Change From Baseline in PEF as Measured by Spirometry at Week 144	0.23 L/sec Standard Deviation 1.099

SECONDARY outcome

Timeframe: Baseline, Week 144

PCF measures an individual's maximum speed of expiration during cough.

Outcome measures

Outcome measures
Measure	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 up to 144 weeks.
Change From Baseline in PCF as Measured by Spirometry at Week 144	0.53 L/sec Standard Deviation 1.281

SECONDARY outcome

Timeframe: Baseline, Week 144

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 domain was prespecified in the protocol for analysis:Transfers/Basic Mobility domain assesses difficulty experienced in performing routine motor activities in daily life. 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	Ataluren n=65 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 up to 144 weeks.
Change From Baseline in PODCI Transfers/Basic Mobility Score at Week 144	-29.3 units on a scale Standard Deviation 25.05

SECONDARY outcome

Timeframe: Baseline, Week 144

Population: AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. 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 144), 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 better), 2 (slightly better), 3 (unchanged), 4 (slightly worse), or 5 (much worse).

Outcome measures

Outcome measures
Measure	Ataluren n=218 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 up to 144 weeks.
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Walking · Much worse	55 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Other · Slightly worse	13 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Walking · Much better	6 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Walking · Slightly better	3 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Walking · Unchanged	47 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Walking · Slightly worse	32 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Climbing Stairs · Much better	6 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Climbing Stairs · Slightly better	4 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Climbing Stairs · Unchanged	37 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Climbing Stairs · Slightly worse	29 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Climbing Stairs · Much worse	65 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Upper Extremity Activity · Much better	5 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Upper Extremity Activity · Slightly better	6 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Upper Extremity Activity · Unchanged	75 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Upper Extremity Activity · Slightly worse	21 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Upper Extremity Activity · Much worse	12 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Other · Much better	3 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Other · Slightly better	2 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Other · Unchanged	29 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Physical Functioning: Other · Much worse	15 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Emotional/Social Functioning · Much better	13 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Emotional/Social Functioning · Slightly better	16 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Emotional/Social Functioning · Unchanged	93 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Emotional/Social Functioning · Slightly worse	7 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Emotional/Social Functioning · Much worse	5 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Cognition/Social Functioning · Much better	9 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Cognition/Social Functioning · Slightly better	24 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Cognition/Social Functioning · Unchanged	92 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Cognition/Social Functioning · Slightly worse	8 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Cognition/Social Functioning · Much worse	0 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel General Energy Level · Much better	8 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel General Energy Level · Slightly better	8 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel General Energy Level · Unchanged	82 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel General Energy Level · Slightly worse	21 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel General Energy Level · Much worse	8 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Sleep · Much better	11 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Sleep · Slightly better	11 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Sleep · Unchanged	95 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Sleep · Slightly worse	9 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Sleep · Much worse	2 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Other · Much better	2 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Other · Slightly better	2 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Other · Unchanged	12 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Other · Slightly worse	8 Participants
Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel Other · Much worse	7 Participants

SECONDARY outcome

Timeframe: Pre-dose at Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144

Population: AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

Pre-dose ataluren plasma concentrations prior to morning ataluren administration at each clinic visit was assessed using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC/MS-MS) method.

Outcome measures

Outcome measures
Measure	Ataluren n=218 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 up to 144 weeks.
Ataluren Plasma Concentration Week 12	4.5231 micrograms/milliliter (μg/mL) Standard Deviation 5.08583
Ataluren Plasma Concentration Week 24	4.4817 micrograms/milliliter (μg/mL) Standard Deviation 5.65883
Ataluren Plasma Concentration Week 36	5.1551 micrograms/milliliter (μg/mL) Standard Deviation 5.67555
Ataluren Plasma Concentration Week 48	5.2221 micrograms/milliliter (μg/mL) Standard Deviation 5.32846
Ataluren Plasma Concentration Week 60	5.0396 micrograms/milliliter (μg/mL) Standard Deviation 5.07812
Ataluren Plasma Concentration Week 72	6.0677 micrograms/milliliter (μg/mL) Standard Deviation 6.05912
Ataluren Plasma Concentration Week 84	5.4673 micrograms/milliliter (μg/mL) Standard Deviation 5.15083
Ataluren Plasma Concentration Week 96	5.8870 micrograms/milliliter (μg/mL) Standard Deviation 5.90954
Ataluren Plasma Concentration Week 108	5.5905 micrograms/milliliter (μg/mL) Standard Deviation 6.48016
Ataluren Plasma Concentration Week 120	5.2406 micrograms/milliliter (μg/mL) Standard Deviation 5.69648
Ataluren Plasma Concentration Week 132	6.6729 micrograms/milliliter (μg/mL) Standard Deviation 7.03882
Ataluren Plasma Concentration Week 144	5.3898 micrograms/milliliter (μg/mL) Standard Deviation 6.28487

SECONDARY outcome

Timeframe: Baseline, Week 144

Blood pressure determination was performed with the participant in a sitting position after a 5-minute rest.

Outcome measures

Outcome measures
Measure	Ataluren n=68 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 up to 144 weeks.
Change From Baseline in Systolic and Diastolic Blood Pressure at Week 144 Systolic blood pressure	0.8 mmHg Standard Deviation 11.86
Change From Baseline in Systolic and Diastolic Blood Pressure at Week 144 Diastolic blood pressure	1.3 mmHg Standard Deviation 11.60

SECONDARY outcome

Timeframe: Baseline, Week 144

Pulse rate determination was performed with the participant in a sitting position after a 5-minute rest.

Outcome measures

Outcome measures
Measure	Ataluren n=68 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 up to 144 weeks.
Change From Baseline in Pulse Rate at Week 144	-0.9 beats/minute Standard Deviation 13.00

SECONDARY outcome

Timeframe: Baseline, Week 144

Outcome measures

Outcome measures
Measure	Ataluren n=68 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 up to 144 weeks.
Change From Baseline in Body Temperature at Week 144	0.05 degrees centigrade Standard Deviation 0.545

Adverse Events

Ataluren

Serious events: 24 serious events

Other events: 201 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ataluren n=218 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 up to 144 weeks.
Injury, poisoning and procedural complications Exposure to communicable disease	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Injury, poisoning and procedural complications Femur fracture	2.3% 5/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Injury, poisoning and procedural complications Hip fracture	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Injury, poisoning and procedural complications Laceration	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.92% 2/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Injury, poisoning and procedural complications Spinal compression fracture	0.92% 2/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Infections and infestations Adenoiditis	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Infections and infestations Appendicitis	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Infections and infestations Chronic sinusitis	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Infections and infestations Gastroenteritis	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Infections and infestations Pneumonia	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Infections and infestations Tonsillitis	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Infections and infestations Urinary tract infection	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Infections and infestations Varicella	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Gastrointestinal disorders Colitis	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Gastrointestinal disorders Colitis ulcerative	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Gastrointestinal disorders Gastritis	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Gastrointestinal disorders Intussusception	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Musculoskeletal and connective tissue disorders Flank pain	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Musculoskeletal and connective tissue disorders Joint contracture	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Musculoskeletal and connective tissue disorders Tendinous contracture	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.92% 2/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Respiratory, thoracic and mediastinal disorders Pulmonary artery stenosis	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Cardiac disorders Bradycardia	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Congenital, familial and genetic disorders Transposition of the great vessels	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Congenital, familial and genetic disorders Ventricular septal defect	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Eye disorders Cataract	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Immune system disorders Drug hypersensitivity	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Metabolism and nutrition disorders Hypocalcaemia	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Renal and urinary disorders Nephrolithiasis	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Vascular disorders Hypotension	0.46% 1/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.

Other adverse events

Other adverse events
Measure	Ataluren n=218 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 up to 144 weeks.
Infections and infestations Ear infection	5.0% 11/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Infections and infestations Gastroenteritis	8.3% 18/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Infections and infestations Influenza	10.6% 23/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Infections and infestations Nasopharyngitis	26.1% 57/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Infections and infestations Upper respiratory tract infection	12.8% 28/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Injury, poisoning and procedural complications Fall	22.0% 48/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Injury, poisoning and procedural complications Ligament sprain	8.7% 19/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
General disorders Disease progression	25.7% 56/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
General disorders Pyrexia	11.9% 26/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Gastrointestinal disorders Abdominal pain upper	8.3% 18/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Gastrointestinal disorders Diarrhoea	7.8% 17/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Gastrointestinal disorders Nausea	7.3% 16/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Gastrointestinal disorders Vomiting	17.0% 37/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Musculoskeletal and connective tissue disorders Arthralgia	6.4% 14/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Musculoskeletal and connective tissue disorders Back pain	12.4% 27/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Musculoskeletal and connective tissue disorders Pain in extremity	11.9% 26/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Respiratory, thoracic and mediastinal disorders Cough	11.9% 26/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Nervous system disorders Headache	19.3% 42/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Renal and urinary disorders Haematuria	9.2% 20/218 • Baseline (Day 1) up to 6 weeks post-treatment (Week 150) AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.

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