Study of Ataluren in ≥2 to <5 Year-Old Male Participants With Duchenne Muscular Dystrophy

• Sponsor: PTC Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02819557
• Collaborator: (none)
• Enrollment: 14
• Locations: 6
• Arm: 1
• Actual Duration (Months): 20
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase 2, multiple-dose, open-label study evaluating the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ataluren in participants aged ≥2 to <5 years old with Duchenne muscular dystrophy (DMD) caused by a nonsense mutation in the dystrophin gene.

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

Detailed Description

In nonsense mutation DMD (nmDMD), early start of treatment is important and necessary and, therefore, it is relevant to understand the correct and tolerable dose in this age group, particularly since ataluren is dosed by weight. This study included a 4-week screening period, a 52-week treatment period (the first 4 weeks of which included PK parameters), and a 4-week follow-up period for participants who completed the treatment period (60 weeks total duration). The objective of the extension period (treatment period after PK parameters have been completed) was to assess the long-term safety of chronic administration of ataluren in this participant population.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Ataluren (PTC124®) in Patients Aged ≥2 to <5 Years Old With Nonsense Mutation Dystrophinopathy
• Actual Study Start Date: Jun 9, 2016
• Actual Primary Completion Date: Feb 9, 2018
• Actual Study Completion Date: Feb 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ataluren Participants will be administered ataluren orally at a dose of 10 milligrams/kilograms (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose will be provided based upon the weight of each participant, which will be assessed every 12 weeks.	Drug: Ataluren; White to off-white powder for oral suspension.; Other Names: PTC124 Translarna

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment Emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious Adverse Events (SAEs) [Baseline up to Week 56]

   A TEAE was any untoward medical occurrence or undesirable event that begins or worsens following administration of study drug, whether or not considered related to study drug by Investigator. An SAE was an adverse event (AE) resulting in any of the following outcomes or deemed significant for any other reason, death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying) or persistent or significant disability/incapacity not related to dystrophinopathy. An event was not reported as an SAE, if event was exclusively a relapse or expected change or progression of baseline dystrophinopathy. AEs included both SAEs and nonserious AEs. AEs classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and coded using Medical Dictionary for Regulatory Activities. A summary of SAEs and all non-serious AEs, regardless of causality, is located in the Reported Adverse Events section.

2. Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Biochemistry, Hematology, and Urinalysis) Parameter [Baseline up to Week 56]

   Clinical laboratory results that were considered clinically meaningful were to be determined by the Investigator and Sponsor. Biochemistry parameters included sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, magnesium, calcium, phosphorus, uric acid, glucose, total protein, albumin, bilirubin (total, direct, and indirect), aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, lactate dehydrogenase, alkaline phosphatase, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and cystatin C. Hematology parameters included white blood cell count with differential, hemoglobin, hematocrit, other red cell parameters, and platelet count. Urinalysis parameters included pH, specific gravity, glucose, ketones, blood, protein, urobilinogen, bilirubin, nitrite, and leukocyte esterase. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

3. Number of Participants With a Clinically Meaningful Abnormal Electrocardiogram (ECG) Test Results [Baseline up to Week 56]

   ECG results that were considered clinically meaningful were to be determined by the Investigator. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

4. Number of Participants With a Dose-Limiting Toxicity as Measured by Hepatic and Renal Toxicity [Baseline up to Week 56]

   Dose-limiting toxicity was measured through clinical evaluations for potential hepatic and renal toxicities. The clinical evaluations included the following: Hepatic: The participant's medical history, hepatitis screening results, all clinical blood values (particularly serum bilirubin, gamma-glutamyl transferase [GGT], aspartate aminotransferase [AST], and alanine aminotransferase [ALT] values), and all concomitant medications were reviewed. Renal: The participant's medical history, all clinical blood and urine renal values, serum electrolytes, medications, and potential pre- or post-renal conditions were reviewed.

Secondary Outcome Measures

1. Pharmacokinetics: Maximum Observed Plasma Concentration From Time Zero up to 6 Hours After the Morning Dose (Cmax0-6hr) [0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28]

   Ataluren concentrations in plasma were analyzed using a validated high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method.

2. Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration From Time Zero up to 6 Hours After the Morning Dose (Tmax0-6hr) [0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28]

   Ataluren concentrations in plasma were analyzed using a validated HPLC-MS/MS method.

3. Area Under the Plasma Concentration Time Curve From Time Zero up to 10 Hours After the Morning Dose (AUC0-10hr) [0 (predose), 1, 2, 4, 6, 8, and 10 (postdose) hours on Days 1 and 28]

   Ataluren concentrations in plasma were analyzed using a validated HPLC-MS/MS method. AUC0-10hr was measured using the linear trapezoidal rule during the ascending portion of the curve and the log-trapezoidal rule during the descending portion of the curve.

4. Pharmacokinetics: Concentration at the End of the First (Morning) Dose Interval (Ctrough6hr) [0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28]

   Ataluren concentrations in plasma were analyzed using a validated HPLC-MS/MS method.

5. Change From Baseline in Proximal Muscle Function as Assessed by Speed During TFTs [Baseline, Week 28 and Week 52]

   TFTs included time to stand from supine position (rise to standing), time to run/walk 10 meters (m), and time to ascend/descend 4 stairs. A decrease from baseline reflects faster completion of the functional task and, thus, better muscle function. If the time taken to perform a test exceeded 30 seconds or if a participant could not perform the test due to disease progression (PD), a value of 30 seconds was used.

6. Change From Baseline in Physical Function as Measured by the NSAA [Baseline, Week 28 and Week 52]

   NSAA consists of 17 activities, including items assessing abilities necessary to remain functionally ambulant (that is, ability to rise from floor, to get from lying to sitting/sitting to standing, and that are known to progressively deteriorate); items that can be partly present in DMD early stages (that is, assessing head raise and standing on heels); and a number of activities such as hopping, jumping, and running. Since the boys were <5 years old, revised 16 point, 8-point, and 3-point scales were used over the 17 point scale. Scores for evaluations=0 (Unable to achieve independently), 1 (Modified method but achieved goal independent of physical assistance), or 2 (Normal, no obvious modification of activity). Maximum total score for the 16-point scale=32, 8-point scale=16, and 3-point scale=6. If an activity couldn't be performed due to PD/loss of ambulation, a score of 0 was assigned. Change from Baseline calculated by subtracting Baseline value from value at Week 28 and Week 52.

7. Change From Baseline in Height of Participants at Weeks 4, 16, 28, 40, 52, and 56 [Baseline, Weeks 4, 16, 28, 40, 52, and 56]

8. Change From Baseline in Weight of Participants at Weeks 4, 16, 28, 40, 52, and 56 [Baseline, Weeks 4, 16, 28, 40, 52, and 56]

9. Change From Baseline in Body Mass Index of Participants at Weeks 4, 16, 28, 40, 52, and 56 [Baseline, Weeks 4, 16, 28, 40, 52, and 56]

   Body mass index is an estimate of body fat based on body weight divided by height squared.

10. Ataluren Palatability Characteristics as Determined by a Parent/Caregiver Questionnaire [Baseline up to Week 28]

    To assess palatability characteristics, participants/parents or guardians were asked to provide a response of "Strongly disagree", "Disagree", "Neither agree or disagree", "Agree", or "Strongly Agree" to the following 3 questions: Question 1. "Is the medicine palatable?" Question 2. "On the basis of reaction / facial expression of your child, do you think that the medication is pleasant?" Question 3."You sometimes have problems in giving the medication to your child because he/she refuses to take it or throws it up?"

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 5 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males ≥2 to <5 years of age

• Body weight ≥12 kg

• Diagnosis of DMD

• Nonsense mutation in at least 1 allele of the dystrophin gene

Exclusion Criteria:

• Participation in any other drug or device clinical investigation

• Ongoing use of prohibited concomitant medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Child Neuro NWF	Gulf Breeze	Florida	United States	32561
2	Rush University Medical Center	Chicago	Illinois	United States	60612
3	Children's Hospital Boston	Boston	Massachusetts	United States	02115
4	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
5	Children's Medical Center Dallas	Dallas	Texas	United States	75390-8843
6	University of Utah	Salt Lake City	Utah	United States	84112

Sponsors and Collaborators

• PTC Therapeutics

Investigators

• Study Director: Francesco Bibbiani, MD, PTC Therapeutics

Study Documents (Full-Text)

• Study Protocol - Jan 28, 2016
• Statistical Analysis Plan - Mar 19, 2018

More Information

Publications

None provided.

• Responsible Party: PTC Therapeutics
• ClinicalTrials.gov Identifier: NCT02819557
• Other Study ID Numbers: PTC124-GD-030-DMD
• First Posted: Jun 30, 2016
• Last Update Posted: Aug 28, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne

Study Results

Participant Flow

Recruitment Details	Participants aged ≥2 to <5 years old with Duchenne muscular dystrophy (DMD) caused by a nonsense mutation in the dystrophin gene were recruited for this study.
Pre-assignment Detail	Participants in the Evaluable Population included all participants who received at least 1 dose of ataluren and had a baseline and at least 1 postbaseline measurement for Timed Function Test (TFT), North Star Ambulatory Assessment (NSAA), or response to the palatability of ataluren questions.

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 milligrams/kilograms (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Period Title: Overall Study
STARTED	14
Safety Population	14
Pharmacokinetics (PK) Population	14
Evaluable Population	14
COMPLETED	14
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Overall Participants	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.4 (0.76)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	14 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 21.4%
Not Hispanic or Latino	11 78.6%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 21.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	11 78.6%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious Adverse Events (SAEs)
Description	A TEAE was any untoward medical occurrence or undesirable event that begins or worsens following administration of study drug, whether or not considered related to study drug by Investigator. An SAE was an adverse event (AE) resulting in any of the following outcomes or deemed significant for any other reason, death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying) or persistent or significant disability/incapacity not related to dystrophinopathy. An event was not reported as an SAE, if event was exclusively a relapse or expected change or progression of baseline dystrophinopathy. AEs included both SAEs and nonserious AEs. AEs classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and coded using Medical Dictionary for Regulatory Activities. A summary of SAEs and all non-serious AEs, regardless of causality, is located in the Reported Adverse Events section.
Time Frame	Baseline up to Week 56

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ataluren (Safety Population).

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Measure Participants	14
At least 1 TEAE	14 100%
Mild TEAE	5 35.7%
Moderate TEAE	8 57.1%
Severe TEAE	1 7.1%
TEAE Related to Study Drug	5 35.7%
TEAE Leading to Participant Study Discontinuation	0 0%
Serious TEAE	0 0%

2. Primary Outcome

Title	Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Biochemistry, Hematology, and Urinalysis) Parameter
Description	Clinical laboratory results that were considered clinically meaningful were to be determined by the Investigator and Sponsor. Biochemistry parameters included sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, magnesium, calcium, phosphorus, uric acid, glucose, total protein, albumin, bilirubin (total, direct, and indirect), aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, lactate dehydrogenase, alkaline phosphatase, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and cystatin C. Hematology parameters included white blood cell count with differential, hemoglobin, hematocrit, other red cell parameters, and platelet count. Urinalysis parameters included pH, specific gravity, glucose, ketones, blood, protein, urobilinogen, bilirubin, nitrite, and leukocyte esterase. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Baseline up to Week 56

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ataluren (Safety Population).

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Measure Participants	14
Count of Participants [Participants]	0 0%

3. Primary Outcome

Title	Number of Participants With a Clinically Meaningful Abnormal Electrocardiogram (ECG) Test Results
Description	ECG results that were considered clinically meaningful were to be determined by the Investigator. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Baseline up to Week 56

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ataluren (Safety Population).

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Measure Participants	14
Count of Participants [Participants]	0 0%

4. Primary Outcome

Title	Number of Participants With a Dose-Limiting Toxicity as Measured by Hepatic and Renal Toxicity
Description	Dose-limiting toxicity was measured through clinical evaluations for potential hepatic and renal toxicities. The clinical evaluations included the following: Hepatic: The participant's medical history, hepatitis screening results, all clinical blood values (particularly serum bilirubin, gamma-glutamyl transferase [GGT], aspartate aminotransferase [AST], and alanine aminotransferase [ALT] values), and all concomitant medications were reviewed. Renal: The participant's medical history, all clinical blood and urine renal values, serum electrolytes, medications, and potential pre- or post-renal conditions were reviewed.
Time Frame	Baseline up to Week 56

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ataluren (Safety Population).

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Measure Participants	14
Number [participants]	0 0%

5. Secondary Outcome

Title	Pharmacokinetics: Maximum Observed Plasma Concentration From Time Zero up to 6 Hours After the Morning Dose (Cmax0-6hr)
Description	Ataluren concentrations in plasma were analyzed using a validated high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method.
Time Frame	0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ataluren and had at least 1 PK concentration datum (PK Population).

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Measure Participants	14
Day 1	15.95 (9.51)
Day 28	12.54 (4.43)

6. Secondary Outcome

Title	Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration From Time Zero up to 6 Hours After the Morning Dose (Tmax0-6hr)
Description	Ataluren concentrations in plasma were analyzed using a validated HPLC-MS/MS method.
Time Frame	0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ataluren and had at least 1 PK concentration datum (PK Population).

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Measure Participants	14
Day 1	3.84 (1.82)
Day 28	2.72 (1.98)

7. Secondary Outcome

Title	Area Under the Plasma Concentration Time Curve From Time Zero up to 10 Hours After the Morning Dose (AUC0-10hr)
Description	Ataluren concentrations in plasma were analyzed using a validated HPLC-MS/MS method. AUC0-10hr was measured using the linear trapezoidal rule during the ascending portion of the curve and the log-trapezoidal rule during the descending portion of the curve.
Time Frame	0 (predose), 1, 2, 4, 6, 8, and 10 (postdose) hours on Days 1 and 28

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ataluren and had at least 1 PK concentration datum (PK Population).

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Measure Participants	14
Day 1	101.64 (58.52)
Day 28	82.13 (27.43)

8. Secondary Outcome

Title	Pharmacokinetics: Concentration at the End of the First (Morning) Dose Interval (Ctrough6hr)
Description	Ataluren concentrations in plasma were analyzed using a validated HPLC-MS/MS method.
Time Frame	0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ataluren and had at least 1 PK concentration datum (PK Population).

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Measure Participants	14
Day 1	9.12 (8.88)
Day 28	5.43 (3.15)

9. Secondary Outcome

Title	Change From Baseline in Proximal Muscle Function as Assessed by Speed During TFTs
Description	TFTs included time to stand from supine position (rise to standing), time to run/walk 10 meters (m), and time to ascend/descend 4 stairs. A decrease from baseline reflects faster completion of the functional task and, thus, better muscle function. If the time taken to perform a test exceeded 30 seconds or if a participant could not perform the test due to disease progression (PD), a value of 30 seconds was used.
Time Frame	Baseline, Week 28 and Week 52

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ataluren and had a baseline and at least 1 postbaseline measurement for TFT, NSAA, or response to the palatability of ataluren questions (Evaluable Population) and had evaluable data for the applicable timed function test.

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Measure Participants	14
Rise to Standing, Baseline	7.2 (7.21)
Rise to Standing, Change from Baseline at Week 28	-3.1 (6.47)
Rise to Standing, Change from Baseline at Week 52	-3.1 (6.50)
Walk/Run 10 m, Baseline	6.6 (2.37)
Walk/Run 10 m, Change from Baseline at Week 28	-0.8 (1.54)
Walk/Run 10 m, Change from Baseline at Week 52	-1.1 (1.35)
Ascend 4 Stairs, Baseline	7.1 (6.95)
Ascend 4 Stairs, Change from Baseline at Week 28	-1.8 (4.85)
Ascend 4 Stairs, Change from Baseline at Week 52	-2.6 (5.00)
Descend 4 Stairs, Baseline	7.5 (3.95)
Descend 4 Stairs, Change from Baseline at Week 28	-0.6 (1.93)
Descend 4 Stairs, Change from Baseline at Week 52	-2.2 (2.58)

10. Secondary Outcome

Title	Change From Baseline in Physical Function as Measured by the NSAA
Description	NSAA consists of 17 activities, including items assessing abilities necessary to remain functionally ambulant (that is, ability to rise from floor, to get from lying to sitting/sitting to standing, and that are known to progressively deteriorate); items that can be partly present in DMD early stages (that is, assessing head raise and standing on heels); and a number of activities such as hopping, jumping, and running. Since the boys were <5 years old, revised 16 point, 8-point, and 3-point scales were used over the 17 point scale. Scores for evaluations=0 (Unable to achieve independently), 1 (Modified method but achieved goal independent of physical assistance), or 2 (Normal, no obvious modification of activity). Maximum total score for the 16-point scale=32, 8-point scale=16, and 3-point scale=6. If an activity couldn't be performed due to PD/loss of ambulation, a score of 0 was assigned. Change from Baseline calculated by subtracting Baseline value from value at Week 28 and Week 52.
Time Frame	Baseline, Week 28 and Week 52

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ataluren and had a baseline and at least 1 postbaseline measurement for TFT, NSAA, or response to the palatability of ataluren questions (Evaluable Population) and had evaluable NSAA data.

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Measure Participants	14
16-Point Scale, Baseline	16.0 (4.66)
16-Point Scale, Change from Baseline at Week 28	3.5 (3.43)
16-Point Scale, Change from Baseline at Week 52	5.5 (4.43)
8-Point Scale, Baseline	10.5 (2.56)
8-Point Scale, Change from Baseline at Week 28	1.5 (1.39)
8-Point Scale, Change from Baseline at Week 52	2.3 (2.13)
3-Point Scale, Baseline	5.4 (0.63)
3-Point Scale, Change from Baseline at Week 28	0.5 (0.78)
3-Point Scale, Change from Baseline at Week 52	0.3 (0.73)

11. Secondary Outcome

Title	Change From Baseline in Height of Participants at Weeks 4, 16, 28, 40, 52, and 56
Time Frame	Baseline, Weeks 4, 16, 28, 40, 52, and 56

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ataluren (Safety Population) and had evaluable height data.

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Measure Participants	14
Baseline	99.43 (5.278)
Change at Week 4	0.83 (1.595)
Change at Week 16	1.84 (1.466)
Change at Week 28	3.11 (1.386)
Change at Week 40	3.82 (1.506)
Change at Week 52	5.95 (2.096)
Change at Week 56	6.04 (2.075)

12. Secondary Outcome

Title	Change From Baseline in Weight of Participants at Weeks 4, 16, 28, 40, 52, and 56
Time Frame	Baseline, Weeks 4, 16, 28, 40, 52, and 56

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ataluren (Safety Population) and had evaluable weight data.

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Measure Participants	14
Baseline	16.99 (3.257)
Change at Week 4	-0.04 (0.502)
Change at Week 16	0.73 (0.974)
Change at Week 28	1.16 (0.940)
Change at Week 40	1.39 (0.882)
Change at Week 52	1.90 (1.259)
Change at Week 56	2.13 (1.340)

13. Secondary Outcome

Title	Change From Baseline in Body Mass Index of Participants at Weeks 4, 16, 28, 40, 52, and 56
Description	Body mass index is an estimate of body fat based on body weight divided by height squared.
Time Frame	Baseline, Weeks 4, 16, 28, 40, 52, and 56

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ataluren (Safety Population).

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Measure Participants	14
Baseline	17.094 (2.2196)
Change at Week 4	-0.346 (0.6804)
Change at Week 16	0.026 (0.3822)
Change at Week 28	0.030 (0.5567)
Change at Week 40	0.008 (0.6399)
Change at Week 52	-0.186 (0.9237)
Change at Week 56	0.015 (1.2161)

14. Secondary Outcome

Title	Ataluren Palatability Characteristics as Determined by a Parent/Caregiver Questionnaire
Description	To assess palatability characteristics, participants/parents or guardians were asked to provide a response of "Strongly disagree", "Disagree", "Neither agree or disagree", "Agree", or "Strongly Agree" to the following 3 questions: Question 1. "Is the medicine palatable?" Question 2. "On the basis of reaction / facial expression of your child, do you think that the medication is pleasant?" Question 3."You sometimes have problems in giving the medication to your child because he/she refuses to take it or throws it up?"
Time Frame	Baseline up to Week 28

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of ataluren and had a baseline and at least 1 postbaseline measurement for TFT, NSAA, or response to the palatability of ataluren questions (Evaluable Population).

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
Measure Participants	14
Question 1, Strongly disagree	0 0%
Question 1, Disagree	0 0%
Question 1, Neither Agree nor Disagree	2 14.3%
Question 1, Agree	0 0%
Question 1, Strongly agree	0 0%
Question 1, No Response	12 85.7%
Question 2, Strongly disagree	0 0%
Question 2, Disagree	2 14.3%
Question 2, Neither Agree nor Disagree	2 14.3%
Question 2, Agree	6 42.9%
Question 2, Strongly Agree	4 28.6%
Question 2, No response	0 0%
Question 3, Strongly Disagree	5 35.7%
Question 3, Disagree	7 50%
Question 3, Neither agree or disagree	0 0%
Question 3, Agree	2 14.3%
Question 3, Strongly Agree	0 0%
Question 3, No response	0 0%

Adverse Events

Time Frame	Baseline up to Week 56
Adverse Event Reporting Description	Adverse events were collected from all participants who received at least 1 dose of ataluren (Safety Population).
Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose was provided based upon the weight of each participant, which was assessed every 12 weeks.
All Cause Mortality
	Ataluren
	Affected / at Risk (%)	# Events
Total	0/14 (0%)
Serious Adverse Events
	Ataluren
	Affected / at Risk (%)	# Events
Total	0/14 (0%)
Other (Not Including Serious) Adverse Events
	Ataluren
	Affected / at Risk (%)	# Events
Total	14/14 (100%)
Gastrointestinal disorders
Abdominal Pain Upper	2/14 (14.3%)
Constipation	2/14 (14.3%)
Flatulence	2/14 (14.3%)
Nausea	1/14 (7.1%)
Stomatitis	1/14 (7.1%)
Vomiting	3/14 (21.4%)
General disorders
Fatigue	1/14 (7.1%)
Gait Disturbance	1/14 (7.1%)
Pyrexia	6/14 (42.9%)
Infections and infestations
Bronchitis Viral	1/14 (7.1%)
Conjunctivitis	1/14 (7.1%)
Croup Infectious	1/14 (7.1%)
Ear Infection	5/14 (35.7%)
Gastroenteritis	1/14 (7.1%)
Gastroenteritis Norovirus	1/14 (7.1%)
Gingival Abscess	1/14 (7.1%)
Hordeolum	1/14 (7.1%)
Influenza	2/14 (14.3%)
Nasopharyngitis	4/14 (28.6%)
Pharyngitis Streptococcal	1/14 (7.1%)
Respiratory Tract Infection	1/14 (7.1%)
Rhinitis	1/14 (7.1%)
Upper Respiratory Tract Infection	2/14 (14.3%)
Viral Rash	1/14 (7.1%)
Injury, poisoning and procedural complications
Arthropod Bite	2/14 (14.3%)
Contusion	1/14 (7.1%)
Fall	1/14 (7.1%)
Tibia Fracture	1/14 (7.1%)
Investigations
Hepatic Enzyme Increased	1/14 (7.1%)
Metabolism and nutrition disorders
Decreased Appetite	1/14 (7.1%)
Hyperlipidaemia	1/14 (7.1%)
Metabolic Acidosis	1/14 (7.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/14 (7.1%)
Pain In Extremity	1/14 (7.1%)
Nervous system disorders
Headache	1/14 (7.1%)
Psychiatric disorders
Abnormal Behaviour	1/14 (7.1%)
Enuresis	1/14 (7.1%)
Insomnia	1/14 (7.1%)
Renal and urinary disorders
Chromaturia	1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Cough	3/14 (21.4%)
Epistaxis	1/14 (7.1%)
Rhinorrhoea	1/14 (7.1%)
Tonsillar Hypertrophy	1/14 (7.1%)
Skin and subcutaneous tissue disorders
Hypertrichosis	1/14 (7.1%)
Rash	3/14 (21.4%)
Rash Generalised	1/14 (7.1%)
Urticaria	1/14 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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