An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy

• Sponsor: PTC Therapeutics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02090959
• Collaborator: (none)
• Enrollment: 219
• Locations: 58
• Arm: 1
• Actual Duration (Months): 50.8
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this study is to obtain long term safety data of ataluren in male participants with nonsense mutation dystrophinopathy (who participated and completed a previous Phase 3 study of ataluren [PTC124-GD-020-DMD ]) to augment the overall safety database. Screening and baseline procedures are structured to avoid a gap in treatment between the double-blind study (PTC124-GD-020-DMD) and this extension study.

This study may be further extended by amendment until either ataluren becomes commercially available or the clinical development of ataluren in duchenne muscular dystrophy (DMD) is discontinued.

Condition or Disease	Intervention/Treatment	Phase
Muscular Dystrophy, Duchenne; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn	Drug: Ataluren	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 219 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Extension Study of Ataluren (PTC124) in Patients With Nonsense Mutation Dystrophinopathy
• Actual Study Start Date: Mar 20, 2014
• Actual Primary Completion Date: Jun 12, 2018
• Actual Study Completion Date: Jun 12, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ataluren Participants will receive 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.	Drug: Ataluren; Ataluren will be administered per the dose and schedule specified in the arm.; Other Names: PTC124

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Baseline (Day 1) up to 6 weeks post-treatment (Week 150)]

   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.

2. Number of Participants With Abnormalities in Clinical Laboratory Parameters [Baseline (Day 1) up to 6 weeks post-treatment (Week 150)]

   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]).

Secondary Outcome Measures

1. Change From Baseline in 6MWD at Week 144 [Baseline, Week 144]

   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.

2. Change From Baseline in Time to Stand From Supine Position at Week 144 [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.

3. Change From Baseline in Time to Walk/Run 10 Meters at Week 144 [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.

4. Change From Baseline in Time to Climb 4 Stairs at Week 144 [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.

5. Change From Baseline in Time to Descend 4 Stairs at Week 144 [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.

6. Change From Baseline in Physical Function Total Score as Measured by NSAA at Week 144 [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.

7. Change From Baseline in PUL Total Score at Week 144 [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.

8. Change From Baseline in Percent Predicted FVC as Measured by Spirometry at Week 144 [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.

9. Change From Baseline in Percent Predicted FEV1 as Measured by Spirometry at Week 144 [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.

10. Change From Baseline in PEF as Measured by Spirometry at Week 144 [Baseline, Week 144]

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

11. Change From Baseline in PCF as Measured by Spirometry at Week 144 [Baseline, Week 144]

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

12. Change From Baseline in PODCI Transfers/Basic Mobility Score at Week 144 [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.

13. 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 [Baseline, Week 144]

    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).

14. Ataluren Plasma Concentration [Pre-dose at Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144]

    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.

15. Change From Baseline in Systolic and Diastolic Blood Pressure at Week 144 [Baseline, Week 144]

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

16. Change From Baseline in Pulse Rate at Week 144 [Baseline, Week 144]

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

17. Change From Baseline in Body Temperature at Week 144 [Baseline, Week 144]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 15 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Completion of study treatment in the previous Phase 3, double-blind study (PTC124-GD-020-DMD).

• Evidence of signed and dated informed consent/assent document(s) indicating that the participant (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial. Note: If the study candidate is considered a child under local regulation, a parent or legal guardian must provide written consent prior to initiation of study screening procedures and the study candidate may be required to provide written assent. The rules of the responsible Institutional Review Board/Independent Ethic Committee (IRB/IEC) regarding whether 1 or both parents must provide consent and the appropriate ages for obtaining consent and assent from the participant should be followed.

• In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the period of study drug administration and 6-week follow-up period.

• Willingness and ability to comply with scheduled visits, ataluren administration plan, study procedures, laboratory tests, and study restrictions.

Exclusion Criteria:

• Known hypersensitivity to any of the ingredients or excipients of the study drug (Litesse® UltraTM [refined polydextrose], polyethylene glycol 3350, Lutrol® micro F127 [poloxamer 407], mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, Cab-O-Sil® M5P [colloidal silica], and magnesium stearate).

• Ongoing participation in any other therapeutic clinical trial.

• Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram (ECG) findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles	Los Angeles	California	United States	90095
2	UC Davis Medical Center	Sacramento	California	United States	95817
3	Stanford University Medical Center	Stanford	California	United States	94305
4	Children's Hospital Colorado - Center for Cancer and Blood Disorders	Aurora	Colorado	United States	80045
5	Child Neurology Center of Northwest Florida	Gulf Breeze	Florida	United States	32561
6	Rush University Medical Center	Chicago	Illinois	United States	60612
7	University of Iowa	Iowa City	Iowa	United States	52242
8	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
9	Children's Hospital Boston	Boston	Massachusetts	United States	02115
10	University of Minnesota	Minneapolis	Minnesota	United States	55455
11	Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research	Saint Louis	Missouri	United States	63110
12	Columbia University College of Physicians & Surgeons	New York	New York	United States	10032
13	Children's Hospital Cincinnati	Cincinnati	Ohio	United States	45229
14	Nationwide Children's Hospital	Columbus	Ohio	United States	43209
15	Oregon Health & Science University	Portland	Oregon	United States	97239
16	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
17	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
18	Childrens Medical Center Dallas, Texas	Dallas	Texas	United States	75207
19	Texas Children's Hospital	Houston	Texas	United States	77030
20	University of Utah	Salt Lake City	Utah	United States	84112
21	Seattle Children's Hospital - Childhood Cancer and Blood Disorders	Seattle	Washington	United States	98105
22	The Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
23	The Royal Children's Hospital	Parkville	Victoria	Australia	3052
24	UZ Leuven	Leuven		Belgium	3000
25	Universidade Federal do Rio de Janeiro - Instituto de Puericultura e Pediatria Martagao Gesteira	Rio de Janeiro		Brazil	21.941-912
26	Sao Paulo University -HC/FMUSP	São Paulo		Brazil	05403-900
27	Aleksandrovska Hospital	Sofia		Bulgaria	1431
28	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B 6A8
29	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
30	Children's Hospital of Western Ontario	London	Ontario	Canada	N6C 2RC
31	Hospital Luis Calvo Mackenna	Santiago	Región Metropolitana	Chile
32	Hospital Clinico Universidad Catolica	Santiago		Chile	8330073
33	University Hospital Brno	Brno		Czechia	635 00
34	Motol University Hospital	Praha		Czechia	150 06
35	Hospital de la Timone	Marseille		France	13385
36	CHU de Nantes	Nantes Cedex 1		France	44093
37	Groupe Hospitalier Pitie-Salpetriere	Paris Cedex 13		France	75651
38	Hopital Necker - Enfants Malades	Paris		France	75015
39	Universitaetsklinikum Essen	Essen		Germany	45122
40	University Medical Center Freiburg	Freiburg		Germany	79106
41	Universitat Munchen - von Haunersche Kinder Clinic	Munchen		Germany	80337
42	Hadassah University Hospital	Jerusalem		Israel	91240
43	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano	Milano		Italy	20122
44	Bambino Gesu Hospital	Rome		Italy	00165
45	U.O. Complessa di Neuropsichiatria Infantile	Rome		Italy	00168
46	Policlinico Universitario G. Martino	Sicily		Italy	98125
47	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
48	Medical University of Warsaw	Warsaw		Poland	502-097
49	Hospital Sant Joan de Deu	Barcelona		Spain	08950
50	Hospital Universitari i Politecnic la Fe	Valencia		Spain	46026
51	Queen Silvia Children's Hospital	Goteburg		Sweden	SE-416 85
52	Astrid Lindgren Childrens Hospital	Stockholm		Sweden	17176
53	CHUV Lausanne	Lausanne		Switzerland	1011
54	Hacettepe Childrens Hospital	Ankara		Turkey	06100
55	Erciyes University Faculty of Medicine	Talas/Kayseri		Turkey	38039
56	University College London Institute of Child Health	London		United Kingdom	WC1N 3JH
57	Royal Manchester Children's Hospital	Manchester		United Kingdom	M13 9WL
58	The Newcastle upon Tyne Hospitals, NHS Foundation Trust	Newcastle upon Tyne		United Kingdom	NE1 3BZ

Sponsors and Collaborators

• PTC Therapeutics

Investigators

• Study Director: Francesco Bibbiani, M.D., PTC Therapeutics

Study Documents (Full-Text)

• Study Protocol - Nov 19, 2015
• Statistical Analysis Plan - Jan 23, 2019

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: PTC Therapeutics
• ClinicalTrials.gov Identifier: NCT02090959
• Other Study ID Numbers: PTC124-GD-020e-DMD
• First Posted: Mar 19, 2014
• Last Update Posted: Aug 11, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by PTC Therapeutics: Duchenne muscular dystrophy; Dystrophinopathy; Nonsense mutation; Premature stop codon; Becker muscular dystrophy; DMD/BMD; PTC124; Ataluren
• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne; Musculoskeletal Diseases; Muscular Diseases; Muscular Disorders, Atrophic; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	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.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Period Title: Overall Study
STARTED	219
As-treated Population	218
COMPLETED	68
NOT COMPLETED	151

Baseline Characteristics

Arm/Group Title	Ataluren
Arm/Group Description	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.
Overall Participants	218
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.9 (1.78)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	218 100%
Race/Ethnicity, Customized (Count of Participants)
White	169 77.5%
Black	2 0.9%
Asian	13 6%
Hispanic	12 5.5%
Other	8 3.7%
Missing	14 6.4%
6 Minute Walk Distance (6MWD) (meters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meters]	349.885 (105.7913)
Time to Stand From Supine Position (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	13.0 (10.34)
Time to Walk/Run 10 Meters (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	9.31 (7.388)
Time to Climb 4 Stairs (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	9.03 (8.939)
Time to Descend 4 Stairs (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	7.52 (8.401)
North Star Ambulatory Assessment (NSAA) Total Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	20.73 (8.513)
Performance Upper Limb (PUL) Total Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	68.7 (4.61)
Percent Predicted Forced Vital Capacity (FVC) (percent predicted FVC) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent predicted FVC]	59.42 (13.843)
Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) (percent predicted FEV1) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent predicted FEV1]	53.76 (12.870)
Peak Expiratory Flow (PEF) (liters/second (L/sec)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [liters/second (L/sec)]	3.36 (1.055)
Peak Cough Flow (PCF) (L/sec) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [L/sec]	3.30 (1.139)
Pediatric Outcomes Data Collection Instrument (PODCI) Transfers/Basic Mobility Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	74.6 (23.66)
Blood Pressure (millimeters of mercury (mm Hg)) [Mean (Standard Deviation) ]
Systolic blood pressure	106.3 (10.72)
Diastolic blood pressure	68.6 (11.01)
Pulse Rate (beats/minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [beats/minute]	97.0 (13.31)
Body Temperature (degrees centigrade) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [degrees centigrade]	36.47 (0.453)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	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.
Time Frame	Baseline (Day 1) up to 6 weeks post-treatment (Week 150)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	218
Any AEs	202 92.7%
SAEs	24 11%
Drug-Related AEs	44 20.2%
AEs Leading to Withdrawal From Study	1 0.5%
Mild AEs	87 39.9%
Moderate AEs	71 32.6%
Severe AEs	42 19.3%
Life-threatening AEs	2 0.9%

2. Primary Outcome

Title	Number of Participants With Abnormalities in Clinical Laboratory Parameters
Description	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]).
Time Frame	Baseline (Day 1) up to 6 weeks post-treatment (Week 150)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	218
Count of Participants [Participants]	29 13.3%

3. Secondary Outcome

Title	Change From Baseline in 6MWD at Week 144
Description	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.
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	26
Mean (Standard Deviation) [meters]	-98.18 (86.604)

4. Secondary Outcome

Title	Change From Baseline in Time to Stand From Supine Position at Week 144
Description	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.
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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 value of this parameter at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	19
Mean (Standard Deviation) [seconds]	5.22 (5.104)

5. Secondary Outcome

Title	Change From Baseline in Time to Walk/Run 10 Meters at Week 144
Description	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.
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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 value of this parameter at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	27
Mean (Standard Deviation) [seconds]	2.29 (1.991)

6. Secondary Outcome

Title	Change From Baseline in Time to Climb 4 Stairs at Week 144
Description	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.
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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 value of this parameter at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	22
Mean (Standard Deviation) [seconds]	4.01 (7.260)

7. Secondary Outcome

Title	Change From Baseline in Time to Descend 4 Stairs at Week 144
Description	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.
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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 value of this parameter at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	22
Mean (Standard Deviation) [seconds]	2.45 (5.853)

8. Secondary Outcome

Title	Change From Baseline in Physical Function Total Score as Measured by NSAA at Week 144
Description	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.
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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 value of this parameter at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	40
Mean (Standard Deviation) [units on a scale]	-7.95 (5.611)

9. Secondary Outcome

Title	Change From Baseline in PUL Total Score at Week 144
Description	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.
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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 value of this parameter at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	44
Mean (Standard Deviation) [units on a scale]	-4.0 (7.49)

10. Secondary Outcome

Title	Change From Baseline in Percent Predicted FVC as Measured by Spirometry at Week 144
Description	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.
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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 value of this parameter at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	63
Mean (Standard Deviation) [percent predicted FVC]	3.51 (14.253)

11. Secondary Outcome

Title	Change From Baseline in Percent Predicted FEV1 as Measured by Spirometry at Week 144
Description	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.
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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 value of this parameter at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	63
Mean (Standard Deviation) [percent predicted FEV1]	1.40 (15.319)

12. Secondary Outcome

Title	Change From Baseline in PEF as Measured by Spirometry at Week 144
Description	PEF was defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated.
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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 value of this parameter at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	65
Mean (Standard Deviation) [L/sec]	0.23 (1.099)

13. Secondary Outcome

Title	Change From Baseline in PCF as Measured by Spirometry at Week 144
Description	PCF measures an individual's maximum speed of expiration during cough.
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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 value of this parameter at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	57
Mean (Standard Deviation) [L/sec]	0.53 (1.281)

14. Secondary Outcome

Title	Change From Baseline in PODCI Transfers/Basic Mobility Score at Week 144
Description	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.
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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 value of this parameter at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	65
Mean (Standard Deviation) [units on a scale]	-29.3 (25.05)

15. Secondary Outcome

Title	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
Description	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).
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	218
Much better	6 2.8%
Slightly better	3 1.4%
Unchanged	47 21.6%
Slightly worse	32 14.7%
Much worse	55 25.2%
Much better	6 2.8%
Slightly better	4 1.8%
Unchanged	37 17%
Slightly worse	29 13.3%
Much worse	65 29.8%
Much better	5 2.3%
Slightly better	6 2.8%
Unchanged	75 34.4%
Slightly worse	21 9.6%
Much worse	12 5.5%
Much better	3 1.4%
Slightly better	2 0.9%
Unchanged	29 13.3%
Slightly worse	13 6%
Much worse	15 6.9%
Much better	13 6%
Slightly better	16 7.3%
Unchanged	93 42.7%
Slightly worse	7 3.2%
Much worse	5 2.3%
Much better	9 4.1%
Slightly better	24 11%
Unchanged	92 42.2%
Slightly worse	8 3.7%
Much worse	0 0%
Much better	8 3.7%
Slightly better	8 3.7%
Unchanged	82 37.6%
Slightly worse	21 9.6%
Much worse	8 3.7%
Much better	11 5%
Slightly better	11 5%
Unchanged	95 43.6%
Slightly worse	9 4.1%
Much worse	2 0.9%
Much better	2 0.9%
Slightly better	2 0.9%
Unchanged	12 5.5%
Slightly worse	8 3.7%
Much worse	7 3.2%

16. Secondary Outcome

Title	Ataluren Plasma Concentration
Description	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.
Time Frame	Pre-dose at Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	218
Week 12	4.5231 (5.08583)
Week 24	4.4817 (5.65883)
Week 36	5.1551 (5.67555)
Week 48	5.2221 (5.32846)
Week 60	5.0396 (5.07812)
Week 72	6.0677 (6.05912)
Week 84	5.4673 (5.15083)
Week 96	5.8870 (5.90954)
Week 108	5.5905 (6.48016)
Week 120	5.2406 (5.69648)
Week 132	6.6729 (7.03882)
Week 144	5.3898 (6.28487)

17. Secondary Outcome

Title	Change From Baseline in Systolic and Diastolic Blood Pressure at Week 144
Description	Blood pressure determination was performed with the participant in a sitting position after a 5-minute rest.
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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 value of this parameter at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	68
Systolic blood pressure	0.8 (11.86)
Diastolic blood pressure	1.3 (11.60)

18. Secondary Outcome

Title	Change From Baseline in Pulse Rate at Week 144
Description	Pulse rate determination was performed with the participant in a sitting position after a 5-minute rest.
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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 value of this parameter at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	68
Mean (Standard Deviation) [beats/minute]	-0.9 (13.00)

19. Secondary Outcome

Title	Change From Baseline in Body Temperature at Week 144
Time Frame	Baseline, Week 144

Outcome Measure Data

Analysis Population Description

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 value of this parameter at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	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.
Measure Participants	68
Mean (Standard Deviation) [degrees centigrade]	0.05 (0.545)

Adverse Events

Time Frame	Baseline (Day 1) up to 6 weeks post-treatment (Week 150)
Adverse Event Reporting Description	AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Arm/Group Title	Ataluren
Arm/Group Description	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.
All Cause Mortality
	Ataluren
	Affected / at Risk (%)	# Events
Total	0/218 (0%)
Serious Adverse Events
	Ataluren
	Affected / at Risk (%)	# Events
Total	24/218 (11%)
Cardiac disorders
Bradycardia	1/218 (0.5%)
Congenital, familial and genetic disorders
Transposition of the great vessels	1/218 (0.5%)
Ventricular septal defect	1/218 (0.5%)
Eye disorders
Cataract	1/218 (0.5%)
Gastrointestinal disorders
Colitis	1/218 (0.5%)
Colitis ulcerative	1/218 (0.5%)
Gastritis	1/218 (0.5%)
Intussusception	1/218 (0.5%)
Immune system disorders
Drug hypersensitivity	1/218 (0.5%)
Infections and infestations
Adenoiditis	1/218 (0.5%)
Appendicitis	1/218 (0.5%)
Chronic sinusitis	1/218 (0.5%)
Gastroenteritis	1/218 (0.5%)
Pneumonia	1/218 (0.5%)
Tonsillitis	1/218 (0.5%)
Urinary tract infection	1/218 (0.5%)
Varicella	1/218 (0.5%)
Injury, poisoning and procedural complications
Exposure to communicable disease	1/218 (0.5%)
Femur fracture	5/218 (2.3%)
Hip fracture	1/218 (0.5%)
Laceration	1/218 (0.5%)
Lumbar vertebral fracture	2/218 (0.9%)
Spinal compression fracture	2/218 (0.9%)
Metabolism and nutrition disorders
Hypocalcaemia	1/218 (0.5%)
Musculoskeletal and connective tissue disorders
Flank pain	1/218 (0.5%)
Joint contracture	1/218 (0.5%)
Tendinous contracture	1/218 (0.5%)
Renal and urinary disorders
Nephrolithiasis	1/218 (0.5%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/218 (0.5%)
Hypoxia	2/218 (0.9%)
Pneumonia aspiration	1/218 (0.5%)
Pulmonary artery stenosis	1/218 (0.5%)
Vascular disorders
Hypotension	1/218 (0.5%)
Other (Not Including Serious) Adverse Events
	Ataluren
	Affected / at Risk (%)	# Events
Total	201/218 (92.2%)
Gastrointestinal disorders
Abdominal pain upper	18/218 (8.3%)
Diarrhoea	17/218 (7.8%)
Nausea	16/218 (7.3%)
Vomiting	37/218 (17%)
General disorders
Disease progression	56/218 (25.7%)
Pyrexia	26/218 (11.9%)
Infections and infestations
Ear infection	11/218 (5%)
Gastroenteritis	18/218 (8.3%)
Influenza	23/218 (10.6%)
Nasopharyngitis	57/218 (26.1%)
Upper respiratory tract infection	28/218 (12.8%)
Injury, poisoning and procedural complications
Fall	48/218 (22%)
Ligament sprain	19/218 (8.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	14/218 (6.4%)
Back pain	27/218 (12.4%)
Pain in extremity	26/218 (11.9%)
Nervous system disorders
Headache	42/218 (19.3%)
Renal and urinary disorders
Haematuria	20/218 (9.2%)
Respiratory, thoracic and mediastinal disorders
Cough	26/218 (11.9%)

Limitations/Caveats

The study was terminated early per Sponsor decision due to commercial availability of ataluren.

More Information

Certain Agreements

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

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