A Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy and Safety Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy and Open-Label Extension
Phase: PHASE3
Conditions: Muscular Dystrophy, Duchenne, Muscular Dystrophies, Muscular Disorders, Atrophic, Muscular Diseases, Musculoskeletal Disease, Neuromuscular Diseases, Nervous System Diseases, Genetic Diseases, X-Linked, Genetic Diseases, Inborn
Sponsor: PTC Therapeutics

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Notice of Proprietary Information: This document contains confidential information owned by or in the 
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reviewing these materials, you agree that this information should not be disclosed to others (except where 
required by applicable law) and should not be used for unauthorized purposes. In the event of an actual or 
suspected breach of this obligation, PTC Therapeutics, Inc. should be notified promptly. 
NCT #: NCT03179631 
CLINICAL PROTOCOL 
A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO- 
CONTROLLED EFFICACY AND SAFETY STUDY OF ATALUREN IN 
PATIENTS WITH NONSENSE MUTATION DUCHENNE MUSCULAR 
DYSTROPHY AND OPEN-LABEL EXTENSION 
PTC124-GD-041-DMD 
21 JULY 2020 
VERSION 4.0 
PTC THERAPEUTICS, INC. 
100 CORPORATE COURT 
SOUTH PLAINFIELD, NJ 07080 USA 

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PTC124-GD-041-DMD 
Clinical Protocol 
 
PROTOCOL IDENTIFIERS AND STUDY PERSONNEL 
 
Project Code 
PTC124-GD 
Therapeutic Area 
Genetic Disorders - Duchenne Muscular Dystrophy 
PTC Therapeutics Substance Identifier 
Ataluren (PTC124) 
IND Number 
68,431 
EudraCT Number 
2017-001223-49 
ClinicalTrials.gov Identifier 
NCT03179631 
Protocol Number 
PTC124-GD-041-DMD 
Protocol Version 
Version 4.0 
Protocol Version Date 
21 July 2020 
Protocol Phase 
Phase 3 
Protocol Title 
A Phase 3, Randomized, Double-Blind, Placebo- 
Controlled Efficacy and Safety Study of Ataluren in 
Patients with Nonsense Mutation Duchenne Muscular 
Dystrophy and Open-Label Extension 
PTC Clinical Lead/Medical Monitor 
 
PTC Therapeutics, Inc. 
100 Corporate Court 
South Plainfield, NJ 07080 USA 
Telephone (office): 
 
Facsimile: 
 
E-mail: 
 
PTC Biostatistician 
 
PTC Therapeutics, Inc. 
100 Corporate Court 
South Plainfield, NJ 07080 USA 
Telephone (office): 
 
Facsimile: 
 
E-mail: 
 
PTC Study Manager 
 
PTC Therapeutics, Inc. 
100 Corporate Court 
South Plainfield, NJ 07080 USA 
Facsimile: 
 
E-mail: 
 

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PTCl24-GD-04 I-DMD 
 Clinical Protocol 
 
 
PTC THERAPEUTICS PROTOCOL APPROVAL SIGNATURES 
 
 
 
 
PT Therapeutics, Inc 
 
 
 
 
 
 
 
PTC Therapeutics, Inc 
 
 
 
 
 
 
PTC Therapeutics, Inc 
Date 
 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
PTC Therapeutics. Inc 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 

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PTC124-GD-041-DMD 
 Clinical Protocol 
 
 
PTC THERAPEUTICS PROTOCOL APPROVAL SIGNATURES 
 
 
 
 
 
 
 
 
PTC Therapeutics, Inc 
Date 
 
 
 
 
 
 
 
PTC Therapeutics, Inc 
Date 
 
 
 
 
 
 
 
 
 
 
PTC Therapeutics, Inc 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PTC124-GD-041-DMD 
Clinical Protocol 
 
PTC THERAPEUTICS PROTOCOL APPROVAL SIGNATURES 
 
 
 
 
 
 
 
 
PTC Terapeutics, Inc 
 
 
 
 
 
PTC Therapeutics, Inc 
 
 
 
 
 
PTC Therapeutics, Inc 
 
PTC Therapeutics, Inc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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PRINCIPAL INVESTIGATOR AGREEMENT AND SIGNATURE 
I have read the protocol document and, on behalf of my institution, agree to comply with 
the protocol and all applicable regulations. 
Principal Investigator 
Date 
Institution: 
Address: 
City: 
State/Province: 
Country: 
Phone: 
Fax: 
Email: 

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TABLE OF CONTENTS 
PROTOCOL IDENTIFIERS AND STUDY PERSONNEL ................................................ 2 
PTC THERAPEUTICS PROTOCOL APPROVAL SIGNATURES ................................. 3 
PRINCIPAL INVESTIGATOR AGREEMENT AND SIGNATURE ................................ 4 
TABLE OF CONTENTS ......................................................................................................... 5 
LIST OF TABLES ................................................................................................................... 9 
LIST OF APPENDICES .......................................................................................................... 9 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ....................................... 10 
1 
INTRODUCTION ................................................................................................. 12 
1.1 
Disease Background .................................................................................. 12 
1.2 
Ataluren ...................................................................................................... 12 
2 
STUDY OBJECTIVE AND ENDPOINTS ......................................................... 13 
2.1 
Objectives ................................................................................................... 13 
2.1.1 
Primary Objective ......................................................................... 13 
2.1.2 
Secondary Objectives .................................................................... 13 
2.1.3 
Exploratory Objectives ................................................................. 13 
2.2 
Endpoints ................................................................................................... 14 
2.2.1 
Double-Blind Treatment Period ................................................... 14 
2.2.1.1 
Primary Endpoint ........................................................... 14 
2.2.1.2 
Secondary Endpoints ...................................................... 14 
2.2.1.3 
Exploratory Endpoints ................................................... 14 
2.2.2 
Open-Label Treatment Period ..................................................... 15 
2.2.2.1 
Secondary Endpoints ...................................................... 15 
2.2.2.2 
Exploratory Endpoints ................................................... 15 
3 
SUBJECT SELECTION CRITERIA .................................................................. 16 
3.1 
Overview ..................................................................................................... 16 
3.2 
Inclusion Criteria....................................................................................... 16 
3.3 
Exclusion Criteria ...................................................................................... 18 
4 
ENROLLMENT PROCEDURES ........................................................................ 19 
4.1 
Source and Number of Subjects ............................................................... 19 
4.2 
Screening .................................................................................................... 19 
4.3 
Randomization and Stratification ............................................................ 19 
4.4 
Blinding ...................................................................................................... 20 
5 
STUDY DRUG ADMINISTRATION ................................................................. 21 
5.1 
Investigational Product ............................................................................. 21 
5.1.1 
Ataluren (PTC124) ........................................................................ 21 
5.1.2 
Placebo ............................................................................................ 21 
5.1.3 
Packaging and Labeling ................................................................ 21 
5.1.4 
Study Drug Dispensing ................................................................. 21 
5.1.5 
Return of Study Drug .................................................................... 22 
5.1.6 
Storage and Stability ..................................................................... 22 

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5.1.7 
Study Drug Accountability ...........................................................22 
5.1.8 
Overdose Precautions ....................................................................23 
5.1.9 
Inadvertent Exposure and Spill Precautions ..............................23 
5.2 
Study Drug Treatment ..............................................................................23 
5.2.1 
Duration of Treatment ..................................................................23 
5.2.2 
Schedule of Administration ..........................................................23 
5.2.3 
Instructions for Delays in Dosing .................................................23 
5.2.4 
Study Drug Preparation and Storage ..........................................24 
5.3 
Safety Monitoring and Study Drug Dose 
Interruption/Modification .........................................................................24 
5.3.1 
Laboratory Abnormalities and Adverse Events Requiring 
Evaluation and Potential Drug Interruption/Modification .......24 
5.3.2 
Evaluation of Adverse Events or Laboratory Abnormalities ....25 
5.3.3 
Instructions for Resuming Study Drug Administration 
after an Interruption for Safety Concerns ..................................25 
5.3.4 
Instructions for Discontinuation of Study Drug 
Administration for Safety Concerns ............................................26 
5.4 
Concomitant and Supportive Therapy ....................................................26 
5.4.1 
Corticosteroids ...............................................................................26 
5.4.2 
Aminoglycosides and Vancomycin ...............................................27 
5.4.3 
Hydration .......................................................................................27 
5.4.4 
Cardiac Drugs for Cardiomyopathy 
Prophylaxis/Treatment ..................................................................28 
5.4.5 
Drugs Metabolized by Cytochrome P450 Enzymes ....................28 
5.4.6 
Other Potential Drug Interactions ...............................................28 
5.4.7 
Other Concomitant Medications ..................................................29 
5.5 
Assistive Devices ........................................................................................29 
5.6 
Physical and Respiratory Therapy ..........................................................29 
5.7 
Dietary Restrictions ...................................................................................29 
6 
SCHEDULE OF EVENTS AND STUDY PARAMETERS ..............................30 
6.1 
Schedule of Events .....................................................................................30 
6.2 
Explanation of Study Procedures .............................................................33 
6.2.1 
Pretreatment, Treatment, and Follow-Up Periods .....................33 
6.2.1.1 
Screening Period ............................................................. 33 
6.2.1.2 
Baseline Treatment Visit (Visit 2) .................................. 33 
6.2.1.3 
Treatment Visits During Study ....................................... 34 
6.2.1.4 
End of Treatment ............................................................ 34 
6.2.1.5 
Post-Treatment Follow-Up Phone Visit.......................... 34 
6.2.2 
Informed Consent ..........................................................................34 
6.2.3 
Clinical/Medication History .........................................................35 
6.2.4 
Hepatitis Screen .............................................................................35 
6.2.5 
Vital Signs ......................................................................................35 
6.2.6 
Height, Weight, and Physical Examination.................................35 
6.2.7 
Genotyping .....................................................................................35 
6.2.8 
Hematology Laboratory Assessment ...........................................36 
6.2.9 
Serum Biochemistry Laboratory Assessment .............................36 

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6.2.10 
Pharmacokinetic Assessment ....................................................... 36 
6.2.11 
Urinalysis ........................................................................................ 36 
6.2.12 
12-Lead ECG ................................................................................. 37 
6.2.13 
Spirometry ..................................................................................... 37 
6.2.14 
Echocardiogram............................................................................. 37 
6.2.15 
Study Drug Randomization .......................................................... 37 
6.2.16 
Study Drug Administration .......................................................... 37 
6.2.17 
Study Drug Compliance ................................................................ 37 
6.2.18 
Adverse Events .............................................................................. 38 
6.2.19 
Concomitant Medications ............................................................. 38 
6.2.20 
Myometry ....................................................................................... 38 
6.2.21 
Performance of Upper Limb ........................................................ 38 
6.2.22 
6-Minute Walk Test ....................................................................... 39 
6.2.23 
North Star Ambulatory Assessment ............................................ 39 
6.2.24 
Timed Function Tests .................................................................... 39 
6.2.25 
DMD Upper Limb PROM ............................................................ 39 
6.2.26 
Magnetic Resonance Imaging/Spectroscopy ............................... 39 
6.2.27 
At-Home Questionnaires ............................................................... 40 
6.3 
Blood Collection Summary ....................................................................... 40 
7 
ADVERSE EVENT ASSESSMENTS .................................................................. 40 
7.1 
Adverse Event Definitions ........................................................................ 40 
7.1.1 
Adverse Events .............................................................................. 40 
7.1.2 
Serious Adverse Events (SAEs) .................................................... 41 
7.1.3 
Unexpected Adverse Events ......................................................... 42 
7.2 
Eliciting Adverse Event Information ....................................................... 42 
7.3 
Adverse Event Recording ......................................................................... 42 
7.4 
Describing Adverse Event Relationship to Study Drug ......................... 43 
7.5 
Grading of Severity of Adverse Events ................................................... 43 
7.6 
Pregnancy of Female Partners ................................................................. 44 
7.7 
Follow-Up of Unresolved Adverse Events ............................................... 45 
7.8 
Adverse Event Reporting Period ............................................................. 45 
7.9 
Investigator Site Adverse Event Reporting Requirements .................... 45 
7.10 
Serious Adverse Event Reporting ............................................................ 45 
7.11 
PTC Therapeutics Adverse Event Reporting Requirements ................ 46 
8 
WITHDRAWAL OF SUBJECTS ........................................................................ 47 
9 
STATISTICS AND DATA MANAGEMENT .................................................... 47 
 
 
9.2 
Study Population Definition ..................................................................... 48 
9.2.1 
Intention-to-Treat (ITT) Population ............................................ 48 
9.2.2 
Modified Intention-to-Treat (mITT) Population ........................ 48 
9.2.3 
As Treated - Population ................................................................ 48 
9.2.4 
Per-Protocol Population ................................................................ 48 
9.2.5 
Evaluable Populations ................................................................... 49 
9.3 
General Statistical Considerations ........................................................... 49 
9.4 
Specific Statistical Analyses ...................................................................... 49 

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9.4.1 
Study Conduct and Subject Disposition ......................................49 
9.4.2 
Baseline Characteristics and Treatment Group 
Comparability ................................................................................49 
9.4.3 
Use of Concomitant Medication and Supportive Therapy ........49 
 
 
 
9.4.5 
Secondary Endpoints ....................................................................50 
9.4.5.1 
Timed Function Tests ...................................................... 50 
 
 
9.4.5.3 
North Star Ambulatory Assessment ............................... 51 
 
 
9.4.7 
Safety ..............................................................................................52 
9.4.8 
Pharmacokinetic analyses .............................................................52 
9.5 
Description and Timing of Analysis .........................................................52 
10 
OBLIGATIONS OF THE INVESTIGATOR AND THE SPONSOR ..............53 
10.1 
Compliance with Ethical and Regulatory Guidelines ............................53 
10.2 
Institutional Review Board/Independent Ethics Committee .................53 
10.3 
Informed Consent/Assent ..........................................................................53 
10.4 
Electronic Case Report Forms .................................................................54 
10.5 
Study Records ............................................................................................54 
10.6 
Confidentiality ...........................................................................................55 
10.7 
Retention of Records .................................................................................55 
10.8 
Monitoring and Auditing ..........................................................................55 
10.9 
Termination of the Study ..........................................................................56 
10.10 
Public Notification of Study Conduct ......................................................56 
10.11 
Dissemination of Results ...........................................................................56 
10.12 
Communication with Regulatory Authorities .........................................57 
11 
RATIONALE FOR STUDY DESIGN FEATURES ..........................................57 
11.1 
Endpoint Selection .....................................................................................57 
11.1.1 
Overview .........................................................................................57 
11.1.2 
6-Minute Walk Test .......................................................................57 
11.1.3 
Timed Function Tests ....................................................................58 
11.1.4 
North Star Ambulatory Assessment ............................................58 
11.1.5 
Myometry .......................................................................................58 
11.1.6 
Performance of Upper Limb (PUL) .............................................58 
11.1.7 
DMD Upper Limb PROM ............................................................59 
11.1.8 
Magnetic Resonance Imaging .......................................................59 
11.1.9 
At-Home Questionnaires ...............................................................60 
11.1.10 
Safety Profiling ..............................................................................60 
11.1.11 
Study Drug Compliance ................................................................60 
11.1.12 
Timing of Assessments ..................................................................60 
11.2 
Subject Selection ........................................................................................61 
11.2.1 
General ...........................................................................................61 
11.2.2 
DMD Diagnosis ..............................................................................61 
11.2.3 
Age ..................................................................................................61 
11.2.4 
Baseline 6MWD .............................................................................62 

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11.2.5 
Baseline Timed Function Tests .................................................... 62 
11.2.6 
Reproductive Considerations ....................................................... 63 
11.2.7 
Prior and Concomitant Therapies ............................................... 63 
11.2.7.1 Corticosteroids ................................................................ 63 
11.2.7.2 Other Prior and Concomitant Therapies ....................... 63 
11.3 
Methods to Reduce Bias ............................................................................ 64 
11.3.1 
Randomization ............................................................................... 64 
11.3.2 
Stratification................................................................................... 64 
11.3.3 
Blinding .......................................................................................... 65 
11.4 
Treatment and Safety Monitoring Plan .................................................. 66 
11.4.1 
Reference Therapy ........................................................................ 66 
11.4.2 
Schedule and Dose Selection ......................................................... 66 
11.4.3 
Duration of Therapy ..................................................................... 66 
11.4.4 
Safety Monitoring .......................................................................... 66 
11.4.5 
Concomitant Therapies ................................................................. 67 
11.5 
Open-Label Treatment Period ................................................................. 67 
12 
PROTOCOL VERSION HISTORY .................................................................... 68 
12.1 
Version 4.0: 21 July 2020 .......................................................................... 68 
12.2 
Version 3.0: 01 August 2019 ..................................................................... 69 
13 
BIBLIOGRAPHY .................................................................................................. 70 
 
 
LIST OF TABLES 
Table 1. 
Corticosteroid Regimens and Doses Recommended or Required .........17 
Table 2. 
Renal Monitoring Parameters and Actions To Be Taken .....................25 
Table 3. 
Schedule of Events (Double-Blind Treatment Period) ...........................31 
Table 4. 
Schedule of Events (Open-Label Treatment Period) .............................32 
Table 5. 
Relationship of Study Drug to Adverse Event ........................................ 43 
Table 6. 
Grading of Adverse Event Severity ......................................................... 44 
Table 7. 
Investigator Site Reporting Requirements for Adverse Events ............ 45 
LIST OF APPENDICES 
APPENDIX 1 
MANAGEMENT OF CORTICOSTEROIDS ........................................ 76 

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
Term 
Definition 
6MWD 
6-minute walk distance 
6MWT 
6-minute walk test 
ACE 
angiotensin-converting enzyme 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
ARB 
angiotensin receptor blockers 
AST 
aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
BB 
Beta-blocker 
Bi-PAP 
bi-level positive airway pressure 
BUN 
blood urea nitrogen 
CD40 
cluster of differentiation 40 
CD-ROM 
compact disk read-only memory 
cGMP 
current good manufacturing practice 
CI 
confidence interval 
CK 
creatine kinase 
CRF 
case report form 
CRO 
contract research organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 enzyme 
DMD 
Duchenne muscular dystrophy 
DMDSAT 
DMD Functional Ability Self-Assessment Tool 
DNA 
deoxyribonucleic acid 
EC 
ethics committee 
ECG 
Electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EMA 
European Medicines Agency 
EQ-5D 
EuroQoL 5-Dimension 
FDA 
Food and Drug Administration 
FVC 
forced vital capacity 
GCP 
good clinical practice 
GGT 
gamma-glutamyl transferase 
HDL 
high-density lipoprotein 
HRQL 
health-related quality of life 
ICH 
International Council for Harmonisation 
ID 
Identification 
IRB 
institutional review board 
IRT 
interactive response technology 
ITT 
intention-to-treat 
IV 
intravenous 
LDH 
lactate dehydrogenase 
LDL 
low-density lipoprotein 
LTBP4 
latent TGF-beta binding protein 4 
MAR 
missing at random 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intention-to-treat 
MMRM 
mixed model for repeated measures 
MRI 
magnetic resonance imaging 
MRS 
magnetic resonance spectroscopy 

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Term 
Definition 
mRNA 
messenger ribonucleic acid 
nmCF 
nonsense mutation cystic fibrosis 
nmDMD 
nonsense mutation Duchenne muscular dystrophy 
NSAA 
North Star Ambulatory Assessment 
OAT1 
organic anion transporter 1 
OAT3 
organic anion transporter 3 
OATP1B3 
organic anion transporting polypeptide 1B3 
PROM 
Patient-Reported Outcome Measure 
PUL 
Performance of Upper Limb 
RSI 
reference safety information 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SOP 
standard operating procedure 
SPP1 
secreted phosphoprotein 1 
TEAE 
treatment-emergent adverse event 
TFTs 
timed function tests 
ULN 
upper limit of normal 
WHODRUG 
World Health Organization Drug Dictionary 

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1 
INTRODUCTION 
1.1 
Disease Background 
Duchenne muscular dystrophy (DMD) is a rare genetic disorder caused by mutations in the 
gene encoding dystrophin, a protein expressed in skeletal, respiratory, and cardiac muscle 
[Bushby 2010a, Bushby 2010b]. The role of the dystrophin protein is to act as a shock 
absorber, bearing the mechanical stresses that occur during muscle contraction, stabilizing 
muscle cell membranes, and protecting muscles from injury [Petrof 1993]. In the absence of 
dystrophin, the stress placed on the membranes during contractions causes them to tear. 
Degeneration of muscle fibers attracts inflammatory cells, ultimately resulting in the 
replacement of healthy muscle with fatty and fibrosis tissue. 
Muscle weakness in the lower-extremity muscles generally becomes apparent in the first few 
years of life, with delays in motor milestones such as attainment of independent walking 
[Bushby 2010a]. Deterioration of ambulation occurs in the first decade of life and 
wheelchair dependency in the teen years [Bushby 2010a]. Muscle weakness eventually 
develops in the upper-extremity muscles as well as respiratory and cardiac muscles, and 
respiratory or cardiac failure typically results in death by the third decade [Passamano 2012]. 
There is no cure for DMD. Treatments aimed at maintaining ambulation for as long as 
possible and managing the musculoskeletal complications of DMD include corticosteroids, 
physical therapy interventions involving gentle exercise and activity, and surgery to prevent 
or minimize lower-limb contractures and deformities [Bushby 2010a, Bushby 2010b]. The 
use of corticosteroids, previously controversial due to side effects, has increased since the 
publication of clinical management guidelines in 2010 strongly urging consideration of 
glucocorticoid therapy in all patients with DMD [Bushby 2010a, Bushby 2010b]. As the 
disease progresses, respiratory (eg, mechanical ventilation) and cardiac (eg, angiotensin- 
converting-enzyme inhibitors) interventions are employed [Bushby 2010a, Bushby 2010b]. 
Approximately 10 to 15% of boys with DMD have the disease due to a nonsense mutation 
[Aarstma-Rus 2006, Bladen 2015]. A nonsense mutation in deoxyribonucleic acid (DNA) 
results in a premature stop codon in the protein-coding region of the corresponding 
messenger ribonucleic acid (mRNA). When a premature stop codon is present, ribosomal 
translation of mRNA is interrupted before a full-length, functional protein is generated. 
1.2 
Ataluren 
Ataluren promotes ribosomal readthrough of premature stop codons, enabling the formation 
of full-length, functional dystrophin protein [Welch 2007]. Because of the role of the 
dystrophin protein, dystrophin restoration therapy would be expected to stabilize or slow 
disease progression in patients with DMD [Merlini 2015]. 
The efficacy and safety of ataluren as a treatment for nonsense mutation Duchenne muscular 
dystrophy (nmDMD) previously were assessed in 2 randomized, double-blind, 
placebo-controlled, 48-week trials (NCT00592553 and NCT01826487, respectively). Data 
from these studies supported conditional marketing authorization of ataluren for the 
treatment of nmDMD in ambulatory patients aged ≥5 years in Europe, with a specific 
obligation to confirm the efficacy and safety of ataluren in this population by conducting a 
randomized, double-blind, placebo-controlled, 72-week study followed by a 72-week open- 

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label extension. This protocol describes the randomized, double-blind, placebo-controlled, 
72-week study and its 72-week open-label extension. 
A detailed description of the chemistry, pharmacology, efficacy, and safety of ataluren is 
provided in the current Investigator’s Brochure. 
2 
STUDY OBJECTIVE AND ENDPOINTS 
2.1 
Objectives 
2.1.1 
Primary Objective 
The primary objective of this study is to determine the effect of ataluren on ambulation and 
endurance as assessed by the 6-minute walk test (6MWT). 
2.1.2 
Secondary Objectives 
The secondary objectives of this study are to: 
● 
Determine the effects of ataluren on ambulation and burst activity as assessed by 
timed function tests 
● 
Determine the effects of ataluren on lower-limb muscle function as assessed by the 
North Star Ambulatory Assessment (NSAA) 
● 
Assess the safety profile of ataluren 
● 
Evaluate the correlation between plasma concentration of ataluren and functional 
outcomes 
● 
Evaluate the plasma pharmacokinetic (PK) profile of ataluren 
2.1.3 
Exploratory Objectives 
The exploratory objectives of this study are to: 
● 
Determine the effects of ataluren on upper-limb muscle function strength as 
assessed by the Performance of Upper Limb (PUL) and by the DMD Upper Limb 
PROM (in subjects ≥7 years old at baseline) 
● 
Determine the effects of ataluren on muscle strength as assessed by myometry 
(in subjects <7 years old at baseline) 
● 
Determine the effects of ataluren on skeletal muscle integrity as assessed by 
magnetic resonance imaging (MRI) (at pre-qualified sites only) 
● 
Determine the effects of ataluren on subject- and parent/caregiver-reported health- 
related quality of life (HRQL) as assessed by at-home questionnaire 
● 
Determine the effects of ataluren on pulmonary function as assessed by forced 
vital capacity (FVC) 

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2.2 
Endpoints 
2.2.1 
Double-Blind Treatment Period 
The efficacy endpoints below focus on the comparison of ataluren versus placebo in the 
double-blind treatment period (baseline to Week 72). 
2.2.1.1 
Primary Endpoint 
The primary endpoint of this study is slope of change in 6-minute walk distance (6MWD) 
over 72 weeks. 
2.2.1.2 
Secondary Endpoints 
● 
Change from baseline to Week 72 in 6MWD 
● 
Composite of average change in times to run/walk 10 meters, climb 4 stairs, and 
descend 4 stairs at Week 72 
● 
Change from baseline to Week 72 in time to run/walk 10 meters 
● 
Change from baseline to Week 72 in time to climb 4 stairs 
● 
Change from baseline to Week 72 in time to descend 4 stairs 
● 
Change from baseline to Week 72 in NSAA total score 
● 
Time to loss of ambulation over 72 weeks 
● 
Time to loss of stair-climbing over 72 weeks 
● 
Time to loss of stair-descending over 72 weeks 
● 
Risk of loss of NSAA items over 72 weeks 
● 
Ataluren safety profile characterized by type, frequency, severity, and relationship 
to study drug of any adverse events (AEs), or of abnormalities of laboratory tests, 
vital signs, physical examinations, or electrocardiograms (ECGs) 
2.2.1.3 
Exploratory Endpoints 
● 
Changes from baseline to Week 72 in PUL total score and domain subscores 
(in subjects ≥7 years old at baseline) 
● 
Change from baseline to Week 72 in DMD Upper Limb PROM total score 
(in subjects ≥7 years old at baseline) 
● 
Risk of loss of DMD Upper Limb PROM items over 72 weeks (in subjects 
≥7 years old at baseline) 
● 
Change from baseline to Week 72 in myometry parameters (in subjects <7 years 
old at baseline) 
● 
Change from baseline to Week 72 in muscle fat fraction as assessed by MRI 
(at pre-qualified sites only) 
● 
Changes from baseline to Week 72 in HRQL as assessed by EQ-5D 

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● 
Change from baseline to Week 72 in FVC 
2.2.2 
Open-Label Treatment Period 
The efficacy endpoints below focus on the comparison of early-start ataluren (subjects 
receiving ataluren from baseline to Week 144) versus delayed start ataluren (subjects 
receiving ataluren from Week 72 to Week 144) across the double-blind and open-label 
treatment periods. 
2.2.2.1 
Secondary Endpoints 
● 
Slope of change in 6MWD over 144 weeks 
● 
Change from baseline to Week 144 in 6MWD 
● 
Composite of average change in times to run/walk 10 meters, climb 4 stairs, and 
descend 4 stairs at Week 144 
● 
Change from baseline to Week 144 in time to run/walk 10 meters 
● 
Change from baseline to Week 144 in time to climb 4 stairs 
● 
Change from baseline to Week 144 in time to descend 4 stairs 
● 
Change from baseline to Week 144 in NSAA total score 
● 
Time to loss of ambulation over 144 weeks 
● 
Time to loss of stair-climbing over 144 weeks 
● 
Time to loss of stair-descending over 144 weeks 
● 
Risk of loss of NSAA items over 144 weeks 
● 
Ataluren safety profile characterized by type, frequency, severity, and relationship 
to study drug of any AEs, or of abnormalities of laboratory tests, vital signs, 
physical examinations, or ECGs 
● 
Plasma PK at pre-morning dose and 2 hours post-morning dose at Week 144 
2.2.2.2 
Exploratory Endpoints 
Exploratory endpoints will include the following: 
● 
Changes from baseline to Week 144 in PUL total score and domain subscores 
(in subjects ≥7 years old at baseline) 
● 
Change from baseline to Week 144 in DMD Upper Limb PROM total score 
(in subjects ≥7 years old at baseline) 
● 
Risk of loss of DMD Upper Limb PROM items over 144 weeks (in subjects 
≥7 years old at baseline) 
● 
Change from baseline to Week 144 in myometry parameters (in subjects <7 years 
old at baseline) 
● 
Change from baseline to Week 144 in muscle fat fraction as assessed by MRI 
(at pre-qualified sites only) 

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● 
Changes from baseline to Week 144 in HRQL as assessed by EQ-5D 
● 
Change from baseline to Week 144 in FVC 
3 
SUBJECT SELECTION CRITERIA 
3.1 
Overview 
The eligibility criteria are designed to allow entry of subjects for whom study participation is 
considered appropriate. All relevant medical and non-medical conditions should be taken 
into consideration when deciding whether this protocol is suitable for a particular subject. 
Eligibility criteria must not be waived by the investigator and conformance to the eligibility 
criteria is subject to review in the case of a good clinical practice (GCP) or a regulatory 
authority audit. 
3.2 
Inclusion Criteria 
Subjects must meet all of the following conditions to be eligible for enrollment into the 
study: 
1. 
Evidence of signed and dated informed consent/assent document(s) indicating that 
the subject (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/ethics committee (IRB/EC) regarding whether one or both parents must 
provide consent and the appropriate ages for obtaining consent and assent from 
the subject should be followed. 
2. 
Male sex. 
3. 
Age ≥5 years. When Version 3 is implemented or approximately 270 subjects have 
enrolled in the study, only subjects aged ≥7 to ≤16 who meet the mITT criteria 
will be eligible to enroll. 
4. 
Phenotypic evidence of DMD based on the onset of characteristic clinical 
symptoms or signs (eg, proximal muscle weakness, waddling gait, and Gowers’ 
maneuver) by 6 years of age and an elevated serum creatine kinase (CK). Medical 
documentation of phenotypic evidence of DMD needs to be provided upon 
request by the PTC Therapeutics medical monitor. 
5. 
Documentation of the presence of a nonsense point mutation in the dystrophin 
gene as determined by gene sequencing. Note: Review and approval of 
documentation by sponsor or designee is required prior to enrollment. 

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6. 
Use of systemic corticosteroids (prednisone/prednisolone or deflazacort) for a 
minimum of 12 months immediately prior to start of study treatment, with no 
significant change in dosage or dosing regimen for a minimum of 3 months 
immediately prior to start of study treatment and a reasonable expectation that 
dosage and dosing regimen will not change significantly for the duration of the 
study. Note: Daily, every other day, high-dose weekend, and intermittent 
regimens permitted only. The doses recommended or required are shown in 
Table 1. Increases in corticosteroid dose to adjust for increases in body weight 
will not exclude a subject from participation. 
Table 1. 
Corticosteroid Regimens and Doses Recommended or Required 
 
Regimen 
Prednisone/Prednisolone 
Deflazacort 
Daily 
0.75 mg/kg (recommended) 
At least 0.3 mg/kg (required) 
0.9 mg/kg (recommended) 
At least 0.3 mg/kg (required) 
Every other day 
0.75-1.25 mg/kg (recommended) 
2 mg/kg (recommended) 
High-dose weekend 
5 mg/kg given each Friday and 
Saturday (recommended) 
Intermittent 
0.75 mg/kg for 10 days alternating 
with 10-20 days off medication 
(recommended) 
0.6 mg/kg on days 1-20 and 
none for the remainder of the 
month (recommended) 
For the daily regimen, 0.3 mg/kg is the minimum acceptable dose but either 0.75 (prednisone/prednisolone) or 
0.5 (deflazacort) mg/kg is preferred. For the other regimens, a recommended dose or dose range is provided 
in the table although no set dose or dose ranges have been clearly accepted as optimum. 
Reference: Bushby 2010a 
7. 
6MWD ≥150 meters at screening, baseline Day 1, and baseline Day 2. When 
Version 3 is implemented or approximately 270 subjects have enrolled in the 
study, only subjects who meet the mITT criteria, 6MWD ≥300 meters at Baseline 
Day 1 or Day 2, and time to stand from supine ≥5 seconds at Baseline Day 1, will 
be eligible to enroll. Note: Personal assistance or use of assistive devices for 
ambulation (eg, short leg braces, long leg braces, or walkers) will not be 
permitted during the 6MWT. 
8. 
Results of the two Baseline 6MWD results must be determined as valid and results 
of the Day 2 Baseline 6MWD must be within 20% of the Day 1 Baseline 6MWD. 
9. 
Baseline 6MWD (maximum of valid Day 1 and Day 2 values) must be no more 
than a 20% reduction from the valid Screening 6MWD. 
10. Ability to perform timed function tests (run/walk 10 meters, climb 4 stairs, 
descend 4 stairs, stand from supine) within 30 seconds at screening and baseline. 
11. In subjects who are sexually active, willingness to abstain from sexual intercourse 
or employ a barrier or medical method of contraception during the study drug 
administration and 4-week follow-up period. 
12. Willingness and ability to comply with scheduled visits, drug administration plan, 
study procedures, laboratory tests, and study restrictions. Note: Psychological, 
social, familial, or geographical factors that might preclude adequate study 
participation (in particular, the ability to satisfactorily perform the 6MWT) 
should be considered. 

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3.3 
Exclusion Criteria 
Prior to study drug administration, it will be confirmed that the subject meets none of the 
following conditions: 
1. 
Any change (initiation, change in type of drug, dose modification, schedule 
modification, interruption, discontinuation, or reinitiation) in 
prophylaxis/treatment for cardiomyopathy within 1 month prior to start of study 
treatment. 
2. 
Ongoing intravenous (IV) aminoglycoside or IV vancomycin therapy. 
3. 
Prior or ongoing therapy with ataluren. 
4. 
Known hypersensitivity to any of the ingredients or excipients of the study drug 
[eg, refined polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 
25C, crospovidone XL10, hydroxyethyl cellulose, colloidal silica, magnesium 
stearate]. 
5. 
Exposure to another investigational drug within 6 months prior to start of study 
treatment, or ongoing participation in any interventional clinical trial. Note: This 
does not apply to patients receiving deflazacort through an expanded access 
program. 
6. 
History of major surgical procedure within 12 weeks prior to start of study 
treatment, or expectation of major surgical procedure (eg, scoliosis surgery) during 
the 72-week placebo-controlled treatment period. 
7. 
Ongoing immunosuppressive therapy (other than corticosteroids). 
8. 
 
Requirement for daytime ventilator assistance or any use of invasive 
mechanical ventilation via tracheostomy. Note: Evening non-invasive 
mechanical ventilation such as use of bi-level positive airway pressure (Bi-PAP) 
therapy is allowed. 
9. 
Uncontrolled clinical symptoms and signs of congestive heart failure (American 
College of Cardiology/American Heart Association Stage C or Stage D) 
[Hunt 2001]. 
10. Elevated serum creatinine or cystatin C at screening. Note: If the initial test result 
is abnormal, it is permissible to re-test serum creatinine or cystatin C and 
randomize the subject if the re-test result is normal. 
11. Positive for hepatitis B core antibody or hepatitis C antibody at screening. 
12. Prior or ongoing medical condition (eg, concomitant illness, psychiatric condition, 
behavioral disorder, alcoholism, drug abuse), medical history, physical findings 
(eg, lower-limb injury that may affect 6MWT performance), ECG findings, or 
laboratory abnormality that, in the investigator’s opinion, could adversely affect 
the safety of the subject, makes it unlikely that the course of treatment or follow- 
up would be completed, or could impair the assessment of study results. 

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4 
ENROLLMENT PROCEDURES 
4.1 
Source and Number of Subjects 
Study candidates comprise patients with nmDMD who are being followed at the participating 
study sites or are referred to the participating study sites. Subjects will be enrolled at 
investigator sites worldwide and will undergo study-specific screening procedures prior to 
enrollment. Approximately 340 subjects, who meet all inclusion criteria and none of the 
exclusion criteria, will be enrolled. A sample size of approximately 340 subjects will 
include approximately 162 subjects who meet the criteria for inclusion in the primary 
analysis population (defined as the modified intention-to-treat [mITT] population in 
Section 9.2.2). 
4.2 
Screening 
The investigator must inform each prospective subject and/or the parent/legal guardian of the 
nature of the study, explain the potential risks, and obtain written informed consent/assent 
from the subject and/or the parent/legal guardian prior to performing any study-related 
screening procedures. At the time the study candidate signs the informed consent/assent and 
completes the Screening 6MWT, a site representative should access the interactive response 
technology (IRT) system to indicate that a candidate is being screened. The site 
representative will need to supply the IRT system with information, including: 
● 
Site number as previously assigned by PTC Therapeutics 
● 
Subject number 
● 
Subject initials (if permitted per local privacy regulations) 
● 
Subject date of birth 
● 
Date of Screening (Visit 1) 
● 
Results of valid 6MWT obtained at Screening 
The IRT system will use this information to maintain a central screening log documenting 
that screening occurred. Upon successful entry of the subject in the IRT system and 
confirmation of all subject eligibility requirements, the subject may proceed to baseline 
procedures. 
4.3 
Randomization and Stratification 
After a subject has completed all screening and baseline assessments and has been confirmed 
to be eligible by the investigator in accordance with the inclusion and exclusion criteria, the 
subject can be randomized into the study. 
In order to obtain a treatment arm assignment for a subject, a site representative will access 
the IRT system. The user will need to supply the IRT system with at least the following 
information so that the system can assign the subject to a treatment group. 
● 
Site number as previously assigned by PTC Therapeutics 
● 
Subject number as previously entered into the IRT system 
● 
Subject initials 

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● 
Subject date of birth 
● 
Type of corticosteroid 
● 
Results of the baseline Day 1 and Day 2 6MWTs in meters 
● 
Result of the baseline time to stand from supine in seconds 
● 
Brother already randomized into the study: yes or no; if yes, subject number of the 
previously randomized brother 
● 
Subject’s weight at baseline in kg 
The IRT system will provide instructions for dispensing study drug (see Section 5.1.4). 
Subjects will be randomized in a 1:1 ratio to 1 of 2 possible treatment assignments: 
● 
Placebo 
● 
Ataluren (10, 10, 20 mg/kg) 
In order to balance treatment allocation by potentially important predictive factors for the 
6MWT, the following stratification factors will be used: 
● 
Type of concomitant corticosteroid use at baseline: (deflazacort versus 
prednisone/prednisolone) 
● 
Maximum of the Day 1 and Day 2 6MWTs performed at baseline: <300 meters 
versus ≥300 to <350 meters versus ≥350 to <400 meters versus ≥400 meters 
● 
Time to stand from supine at baseline: <5 seconds versus ≥5 seconds 
4.4 
Blinding 
During the double-blind treatment period, the identity of the treatments will be concealed by 
the use of a placebo that is matched to the active drug in appearance, taste, odor, packaging, 
labeling, and schedule of administration. Unblinding will only occur in the case of subject 
emergencies before study completion and at the conclusion of the study. Except for 
emergency unblinding, individual subjects, parents/caregivers, and site personnel will not be 
informed of the randomized treatment assignments until the implications of revealing such 
data for the overall ataluren clinical development program have been determined by PTC 
Therapeutics. 
Emergency unblinding should only occur after the principal investigator deems the subject’s 
emergency warrants the unblinding of the treatment. Unblinding of the treatment can only be 
performed by the principal investigator in the IRT system. Unblinding instructions are 
provided in the IRT system instruction manual. 

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5 
STUDY DRUG ADMINISTRATION 
5.1 
Investigational Product 
5.1.1 
Ataluren (PTC124) 
Blinded ataluren (treatment through Week 72) as well as open-label ataluren (treatment from 
Week 73 to Week 144) will be provided as white to off-white granules for oral suspension. 
The drug substance and drug product are manufactured under current good manufacturing 
practice (cGMP) conditions. The formulation includes matrix and suspending agents, 
surfactants, and various excipients that aid in the manufacturing process. The granules for 
oral suspension are packaged in aluminum foil, child-resistant sachets (packets) and supplied 
in dose strengths containing 125, 250, or 1000 mg of the active drug substance. For 
administration, the granules in the sachet may be mixed with water, fruit juice, fruit punch, or 
milk (skim, 1% fat, 2% fat, whole milk, chocolate milk, soy milk, or lactose-free milk), or 
semi-solid food (yogurt, pudding, or applesauce). 
5.1.2 
Placebo 
A white to off-white granules placebo formulation will be provided for oral suspension. The 
placebo formulation has been manufactured under cGMP conditions. The dry granules and 
the liquid suspension of the drug match the active formulation in appearance, odor, and taste. 
The placebo formulation contains excipients similar to those used in the active product. The 
placebo is packaged in the same aluminum-foil, child-resistant sachets using weights and 
volumes to match each of the 125, 250, and 1000 mg dose strengths of active drug sachets. 
5.1.3 
Packaging and Labeling 
Drug kits will be provided, each of which contains sachets of one of the dose strengths (125, 
250, or 1000 mg or matching placebo [during the double-blind treatment period]). Sachets 
and cartons will be color-coded to indicate dosage strength (125 mg - yellow, 250 mg - pink, 
1000 mg - blue). Each kit will have a unique kit identification (ID) number. Labels will be 
provided in appropriate languages as required by each country in which the study is 
conducted. The content of the labeling will be in accordance with local regulatory 
specifications and requirements. 
5.1.4 
Study Drug Dispensing 
During both treatment periods (double-blind and open-label), dosing of study drug will be 
based on milligrams of drug per kilogram of subject body weight and will be adjusted to 
allow for dosing with up to 2 of the available sachet dose strengths (125 mg, 250 mg, and/or 
1000 mg). The sachet dose strengths and number of sachets to be taken per dose will be 
calculated and provided by the IRT system. 
The clinic staff (eg, pharmacist or other qualified person) will be responsible for dispensing 
study drug according to the IRT system directions. At the time of randomization, the IRT 
system will provide the clinic staff with the subject randomization number and the kit ID 
numbers designating the kits to be dispensed. Multiple kits may be dispensed at a single visit 
(maximum of 2 different strengths). 

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During the double-blind treatment period, study drug will be provided for each 12-week 
study period. During the open-label treatment period, study drug will be provided for each 
24-week study period. 
Because of potential changes in subject body weight over time, at Week 24 (Visit 4) and 
every 24 weeks thereafter, a dose adjustment may be made based on the subject’s body 
weight at that visit. Depending upon the magnitude of change in subject body weight since 
baseline, the number and strengths of sachets to be used by the subject may remain the same 
or may be adjusted. 
5.1.5 
Return of Study Drug 
Subjects and/or parents/caregivers should return all used and unused kits, as well as all 
unused sachets, to the study site at each onsite study visit. Study drug dispensing to the 
subjects and the return of any unused study drug for compliance assessments will be 
documented. 
5.1.6 
Storage and Stability 
Kits containing sachets of study drug will be stored at room temperature. The available 
stability data from representative samples support the use of the drug product for 48 months 
when stored at room temperature. The stability of the clinical study samples or 
representative samples may be monitored, as appropriate, to support the clinical study. 
5.1.7 
Study Drug Accountability 
Study personnel must ensure that all study drug supplies are kept in a secure locked area with 
access limited to authorized personnel. Study drug must not be used outside the context of 
this protocol. Under no circumstances should the investigator or site personnel supply study 
drug to other investigators or clinics or allow the study drug supplies to be used other than as 
directed by this protocol. 
The investigator and/or the responsible site personnel must maintain accurate records of the 
receipt of all study drug shipped by PTC Therapeutics or its designee, including, but not 
limited to, the date received, lot number, amount received, amount returned, and the 
disposition of all study drug product. Drug accountability records must also be maintained 
by the site that include the subject’s assigned study number, date and amount of study drug 
dispensed, and relevant lot and sachet numbers. 
Study drug must be returned to PTC Therapeutics or its designee, except where sites are 
required to destroy study drug per their local standard operating procedures (SOPs). Records 
documenting the date of study drug destruction or shipping, relevant sachet numbers, and 
amount shipped should be kept in the investigator site study file. 

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5.1.8 
Overdose Precautions 
For any subject experiencing an overdose (administration of a study drug dose >4 times the 
intended total daily dose level for this protocol [>160 mg/kg/day]), observation for any 
symptomatic side effects should be instituted, and vital signs and biochemical and 
hematological parameters should be followed closely (consistent with the protocol or more 
frequently, as needed). Appropriate supportive management to mitigate adverse effects 
should be initiated. Use of gastric lavage or induction of emesis is not specifically 
recommended nor contraindicated. 
The PTC Therapeutics medical monitor or designee must be contacted if an overdose occurs, 
and the overdose must be reported as an AE according to Section 7.1.1 (or as a serious 
adverse event [SAE] if it meets the applicable criteria for an SAE in Section 7.1.2). 
5.1.9 
Inadvertent Exposure and Spill Precautions 
Reference can be made to the Ataluren Investigator Brochure for current information on 
inadvertent exposures and spill precautions. 
5.2 
Study Drug Treatment 
5.2.1 
Duration of Treatment 
Treatment will comprise continuous daily administration of double-blind ataluren or placebo 
for 72 weeks followed by continuous daily administration of open-label ataluren for an 
additional 72 weeks. 
5.2.2 
Schedule of Administration 
Throughout the study (ie, during the double-blind treatment period and the open-label 
treatment period), study drug should be taken TID – the 1st dose (10 mg/kg) in the morning, 
the 2nd dose (10 mg/kg) at mid-day, and the 3rd dose (20 mg/kg) in the evening. Intervals 
for dosing ideally should be ~6 hours (±1 hour) between morning and mid-day doses, 
~6 hours (±1 hour) between mid-day and evening doses, and ~12 hours (±1 hour) between 
evening doses and the morning dose on the next day. 
5.2.3 
Instructions for Delays in Dosing 
If a subject experiences a delay in the administration of study drug of ≤1 hour, the planned 
dose should be taken with no changes to the subsequent dose schedules. For a subject who 
has a delay of >1 hour but ≤4 hours, the planned dose should be taken; however, all future 
doses for that day should be shifted later by an approximately corresponding amount. For a 
subject who has a delay in administration of study drug of >4 hours, the dose should not be 
taken. Study drug administration may continue but the missed dose should not be made up 
and the planned timing of subsequent study drug dosing should not be altered. 

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5.2.4 
Study Drug Preparation and Storage 
Study drug sachets should be stored at room temperature, away from the reach of children 
until time of reconstitution and should only be opened at the time of dose preparation. The 
full contents of the sachets should be mixed with at least 30 mL (1 ounce) of liquid (water, 
milk, fruit juice, fruit punch), or 3 tablespoons of semi-solid food (yogurt, pudding, or 
applesauce). The prepared dose should be mixed well and stirred for approximately 30 to 
60 seconds before administration. The amount of the liquid can be increased based on 
subject preference. 
Each prepared dose is best administered immediately after preparation. The prepared dose 
should be discarded if not consumed within 24 hours of preparation (if kept refrigerated), or 
within 3 hours of preparation (if kept at room temperature). 
The clinic staff will instruct each subject or parent/caregiver on the specific number of 
sachets to be taken from each kit for each dose and will provide detailed oral directions 
regarding drug preparation. In addition, detailed written drug mixing and dosing instructions 
will be provided to the subject or parent/caregiver when drug supplies are dispensed. 
5.3 
Safety Monitoring and Study Drug Dose Interruption/Modification 
5.3.1 
Laboratory Abnormalities and Adverse Events Requiring Evaluation and 
Potential Drug Interruption/Modification 
Subjects must be monitored closely for AEs or laboratory abnormalities during the course of 
the study. 
For AEs or laboratory abnormalities, the investigator will use judgment in determining 
whether the event or abnormality is clinically significant, whether diagnostic evaluation is 
warranted, and whether potential interruption of study drug treatment is appropriate. In 
general, life-threatening (Grade 4) or severe (Grade 3) AEs or laboratory abnormalities 
should be considered clinically significant, although recurrent or persistent moderate events 
(Grade 2) may also be considered clinically significant in certain circumstances. Reference 
should be made to the latest version of the Common Terminology Criteria for Adverse 
Events (CTCAE) for grading the severity of AEs and laboratory abnormalities. 
Cases of decreased renal function have been observed in patients with nonsense mutation 
cystic fibrosis (nmCF) receiving ataluren and IV aminoglycosides together with other 
antibiotics for cystic fibrosis exacerbations (Section 5.4.2). As a precaution, Table 2 
provides information on actions to be taken in the event that abnormalities are noted in 
specified renal laboratory parameters. Thresholds are provided for interrupting study drug 
immediately or for interrupting study drug after confirmation of a value beyond the 
threshold. For AEs or laboratory abnormalities not listed in Table 2, the investigator should 
use his/her judgment in determining whether the event or abnormality is clinically 
significant, whether diagnostic evaluation is warranted, and whether potential interruption of 
study drug is appropriate. 

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Table 2. 
Renal Monitoring Parameters and Actions To Be Taken 
 
Laboratory Parameter 
Stop Study Drug Immediately, 
Confirm Abnormal Value, 
and Then Start Work-Up 
Stop Study Drug After 
Confirminga Abnormal Value, 
and Then Start Work-Up 
Serum cystatin C 
>2.00 mg/L 
>1.33 – 2.00 mg/L 
Serum creatinine 
≥ Grade 2 (≥1.5 x ULN for age) 
Grade 1 (>ULN – 1.5 x ULN for age) 
Serum BUN 
≥3.0 x ULN 
≥1.5 – 3.0 x ULN 
Abbreviations: BUN = blood urea nitrogen, ULN = upper limit of normal 
a Laboratory abnormalities may be confirmed immediately or at the next scheduled clinic visit based on 
investigator judgment. 
 
5.3.2 
Evaluation of Adverse Events or Laboratory Abnormalities 
The PTC Therapeutics medical monitor or designee should be notified of any AE or 
laboratory abnormality that leads to dose interruption and should be apprised of ancillary 
laboratory or other diagnostic findings and the evolving data from any work-up of the initial 
abnormality. 
Clinical evaluations for potential hepatic and renal toxicities may include the following: 
● 
Hepatic: The 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 should be reviewed. Depending upon changes observed, 
the recommended diagnostic workup may include more frequent monitoring or 
further evaluations for viral hepatitis and immune disorders; tests for 
cholelithiasis; or abdominal ultrasound, computed tomography, MRI, or other 
imaging methods. 
● 
Renal: The medical history, all clinical blood and urine renal values, serum 
electrolytes, medications, and potential pre or- post renal conditions should be 
reviewed. Depending upon the changes observed, recommended diagnostic 
workup may include further evaluations of blood or urine; tests of glomerular 
filtration rate, concentrating ability, or other renal functions; computed 
tomography, MRI, or other imaging methods; and/or renal biopsy. 
5.3.3 
Instructions for Resuming Study Drug Administration after an Interruption 
for Safety Concerns 
In deciding whether to re-institute study drug after a dose interruption for any clinically 
significant safety concern, the investigator in consultation with PTC Therapeutics should 
consider factors such as the following: 
● 
Type and severity of the AE or laboratory abnormality 
● 
The potential causal relationship of study drug 
● 
The subject’s status in terms of DMD and other health conditions 
● 
The ability to monitor for recurrence of the event 
If further evaluation reveals that the AE that led to dose interruption was not related to the 
study drug, study drug may be restarted. 

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If the subject experiences a recurrence of a previous abnormality that led to study drug dose 
interruption or experiences the new occurrence of an unacceptable AE or laboratory 
abnormality, the investigator should interrupt study drug and confer with the PTC 
Therapeutics medical monitor or designee regarding the potential need to discontinue study 
drug permanently. 
5.3.4 
Instructions for Discontinuation of Study Drug Administration for Safety 
Concerns 
If after appropriate consideration of study drug interruption/modification and consultation 
with the PTC Therapeutics medical monitor, it is not appropriate for a subject to continue 
with study treatment, then study drug should be permanently discontinued. After permanent 
discontinuation of study drug for a safety concern, and if the initial event was reported as a 
SAE, then a follow-up SAE report form should be completed. In the case of a treatment 
discontinuation due to an event that is not an SAE, the PTC Therapeutics medical monitor 
should be notified (see Section 7). In addition, details regarding the reasons for 
discontinuation and the AEs leading to the discontinuation should be recorded in the source 
documents and in the appropriate case report form (CRF). The End of Treatment Visit CRF 
should be completed and appropriate follow-up (at ~4 weeks as per protocol or until recovery 
from or stabilization of the AE, whichever comes last) should be instituted. 
5.4 
Concomitant and Supportive Therapy 
Other than the study drug, any treatments (including prescription and non-prescription drugs, 
health foods, herbal remedies, self-prescribed drugs, street drug, tobacco products, or alcohol) 
that are taken by a subject during the screening period, during study drug administration, and 
for 4 weeks after discontinuation of study drug are considered concomitant medications. 
Information regarding any concomitant medications will be collected and documented in the 
concomitant medication CRF page and in the source documents by the clinic staff. 
5.4.1 
Corticosteroids 
Corticosteroid therapy in DMD improves muscle strength and function in the short term 
[Matthews 2016]. To minimize potential confounding effects of changes in corticosteroid 
therapy on the interpretation of study results, the use of these medications must be 
standardized as much as possible during the study. 
A stable and standardized corticosteroid regimen should be maintained during the 72 weeks 
of double-blind study drug treatment. Adjustments in corticosteroid dosage for increases in 
body weight are permitted (only once during the 72-week double-blind study treatment) but 
are not mandatory. Upward adjustments in corticosteroid dose for increases in body weight 
or other reasons should follow recommendations provided in Appendix A. 
If a subject experiences a concerning AE related to systemic corticosteroid use, interventions 
or potential adjustments in the corticosteroid dosage may be considered, as detailed in 
Appendix A. It should be emphasized that reductions in corticosteroid dosage for cosmetic 
or other minor reasons should be avoided. Subjects who require corticosteroid interruption, 
dose modification, or reinstitution may remain on blinded study drug therapy. 

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5.4.2 
Aminoglycosides and Vancomycin 
Ataluren should not be co-administered with IV aminoglycosides (eg, tobramycin, 
gentamicin, amikacin, kanamycin and/or IV vancomycin), based on cases of decreased renal 
function observed in a clinical trial of ataluren in patients with nmCF. Elevations of serum 
creatinine occurred in several nmCF patients treated with ataluren and IV 
aminoglycosides/vancomycin together with other antibiotics for cystic fibrosis exacerbations. 
The serum creatinine elevations resolved in all cases, with discontinuation of the IV 
aminoglycoside/vancomycin, and either continuation or interruption of ataluren. These 
findings suggested that co-administration of ataluren and IV aminoglycosides/vancomycin 
may potentiate the nephrotoxic effect of these antibiotics. For additional details, refer to the 
Investigator Brochure. 
In subjects who require treatment for serious infections, investigators should substitute other 
antibiotics for systemic aminoglycosides/vancomycin when clinically appropriate. For 
subjects requiring systemic antibiotic therapy, IV aminoglycosides/vancomycin may be used 
when medically necessary. However, consideration should be given to use of alternative 
agents if appropriate. If IV aminoglycosides/vancomycin) are administered, study drug must 
be interrupted during the course of these antibiotic treatments. Subjects requiring IV 
aminoglycoside or IV vancomycin therapy should be closely monitored in an appropriate 
setting, such as a hospital. In subjects receiving potentially nephrotoxic agents such as IV 
aminoglycosides or IV vancomycin, antibiotic drug levels (if appropriate) and serum 
creatinine and blood urea nitrogen (BUN) should be followed closely. The antibiotic trough 
level (if appropriate) and creatinine and BUN should be measured within 24 to 48 hours of 
administration of the first antibiotic dose, and further antibiotic dosing should be based on 
these results. Creatinine and BUN should be measured prior to initiating IV aminoglycoside 
or vancomycin therapy and at least weekly during the course of antibiotic treatment. 
5.4.3 
Hydration 
Because of the potential risk of renal dysfunction during periods of dehydration in subjects 
receiving study drug, it is important to encourage study subjects to maintain adequate 
hydration throughout the study. Subjects should be adequately hydrated prior to receiving 
potentially nephrotoxic agents such as IV aminoglycosides or IV vancomycin, and hydration 
status should be carefully monitored throughout the administration of these agents. 
Investigators should be particularly vigilant with subjects who are experiencing nausea, 
vomiting, diarrhea, or fever, or who have laboratory evidence of dehydration. 

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5.4.4 
Cardiac Drugs for Cardiomyopathy Prophylaxis/Treatment 
The use of angiotensin-converting enzyme (ACE) inhibitors for the management of DMD- 
associated cardiomyopathy has become widespread in the DMD population [El-Aloul 2016]. 
In subjects who are unable to tolerate ACE inhibitors, angiotensin receptor blockers (ARBs) 
are sometimes used. Beta-blocker (BB) therapy is sometimes initiated after ACE 
inhibitor/ARB therapy for progressive cardiac decline. Finally, the use of an aldosterone 
antagonist (AA) has recently demonstrated favorable effects on cardiac function in DMD 
[Raman 2015]. Because changes in the use of cardiac drugs could introduce confounding 
influences on the interpretation of efficacy results, such changes should be minimized during 
study drug therapy. 
For subjects who are not on cardiac drugs for the prophylaxis/treatment of cardiomyopathy, 
initiation of such drugs during the 72 weeks of blinded study drug treatment is discouraged 
unless there is a strong medical need. 
For subjects who are on cardiac drugs, they should be on a stable dose for at least 1 month 
prior to randomization and a stable regimen should be maintained during the 72 weeks of 
blinded study drug treatment. Adjustments in dosage or type of drug are permitted to avoid 
symptoms (eg, cough associated with ACE inhibitors) but attempts should be made to avoid 
entirely removing subjects from cardiomyopathy prophylaxis/treatment. Subjects who 
require initiation, interruption, dose modification, or reinstitution of cardiomyopathy 
prophylaxis/treatment may remain on blinded study drug therapy. 
5.4.5 
Drugs Metabolized by Cytochrome P450 Enzymes 
As the primary route of ataluren metabolism is via glucuronidation by UDP- 
glucuronosyltransferase 1-9 (UGT1A9), clinically significant interactions between ataluren 
and co-administered drugs metabolized by cytochrome P450 enzymes (CYPs) are unlikely. 
In particular, ataluren is not an inhibitor of CYP1A2, CYP2B6, CYP2C19, CYP2D6, and 
CYP3A4/5, and does not have induction potential on the major CYP enzymes. 
In vitro, ataluren is a weak inhibitor of CYP2C8 and CYP2C9, but in vivo drug-drug 
interactions mediated by these enzymes are not expected according to the criteria described 
in the European Medicines Agency (EMA) guideline on the investigation of drug interactions 
[EMA 2012]. As an added measure of safety, however, investigators should pay specific 
attention to use of drugs that are known substrates of these enzymes, particularly when such 
drugs may have a low therapeutic index. 
5.4.6 
Other Potential Drug Interactions 
Based on in vitro studies, ataluren is a substrate of UGT1A9. Coadministration with 
rifampin, a strong inducer of metabolic enzymes, including UGT1A9, decreased ataluren 
exposure by 30%. The significance of these findings is unknown. Caution should be 
exercised when ataluren is coadministered with medicinal products that are inducers of 
UGT1A9 (eg, rifampicin). 

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In vitro data indicate that ataluren is an inhibitor of organic anion transporter 1 (OAT1), 
organic anion transporter 3 (OAT3) and organic anion transporting polypeptide 1B3 
(OATP1B3). Caution should be exercised when ataluren is co-administered with e.g.OAT1, 
OAT3, or OATP1B3 (e.g., oseltamivir, acyclovir, ciprofloxacin, captopril, furosemide, 
bumetanide, valsartan, pravastatin, rosuvastatin, atorvastatin, pitavastatin) because of the risk 
of increased plasma concentration of these drugs. 
The investigator is encouraged to consult the PTC medical monitor or designee with 
questions relating to specific drugs and their potential for interactions with ataluren. 
5.4.7 
Other Concomitant Medications 
To the extent possible, administration of any prescription or over-the-counter drug products 
other than study medication should be minimized during the study period. Subjects should 
be discouraged from use of “health supplements” (eg, creatine, glutamine, coenzyme Q), 
herbal remedies, growth hormone, self-prescribed drugs, street drugs, tobacco products, or 
alcohol at any time during clinical studies of ataluren. 
If considered necessary for the subject’s well-being, drugs for concomitant medical 
conditions or for symptom management may be given at the discretion of the investigator. 
The decision to authorize the use of any other drug(s) should take into account subject safety, 
the medical need, the potential for drug interactions, the possibility for masking symptoms of 
a more relevant underlying event, and whether use of a concomitant medication will 
compromise the outcome or integrity of the study. 
Subjects should be instructed about the importance of the need to inform the clinic staff of 
the use of any drugs or remedies (whether prescribed, over-thecounter-, or illicit) before and 
during the course of the study. Information regarding any concomitant drugs taken by a 
subject during the course of the study and the reason for use will be recorded in the source 
documents and in the concomitant medication CRF. 
5.5 
Assistive Devices 
During study-specified 6MWTs, timed function tests, and NSAA evaluations, subjects must 
not use assistive devices (eg, short leg braces, long leg braces, or walkers). 
5.6 
Physical and Respiratory Therapy 
There are neither restrictions nor prescriptions for physical or respiratory therapy during the 
study. Sites should follow recommendations by the DMD Care Considerations Working 
Group [Bushby 2010b] in providing physical therapy support for subjects participating in the 
study. Respiratory care guidelines for DMD as suggested by the American Thoracic Society 
should be followed [Finder 2004]. If changes in the physical or respiratory therapy regimen 
are planned, sites are encouraged to initiate these changes prior to randomization and to 
maintain the same general level of support throughout the duration of the study. 
5.7 
Dietary Restrictions 
There are no specific dietary restrictions in the study. 

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6 
SCHEDULE OF EVENTS AND STUDY PARAMETERS 
6.1 
Schedule of Events 
The proposed types and timing of data to be recorded are described in Table 3 (double-blind 
treatment period) and Table 4 (open-label treatment period). Refer to Section 6.2 for 
cross-referenced explanations of the study procedures described in the tables. 

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Table 3. 
Schedule of Events (Double-Blind Treatment Period) 
 
Study Period 
Screening 
Double-Blind Treatment 
Notes 
Study Week 
-2 weeks 
1 
12 
24 
36 
48 
60 
72 
2-week screening period may be extended by 1 week if 
Visit Window (days) 
±7 
±7 
±7 
±7 
±7 
±7 
necessary to schedule pretreatment MRI 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
8 
At Visit 2, complete assessments before first dose 
Visit Day 
1 
2 
1 
2 
2-day visits only at Visit 2 and Visit 8 
Informed consent 
X 
May be obtained prior to Visit 1 (eg, by phone) 
Enter subject in IRT system 
X 
Access IRT system to enter subject 
Clinical and medication 
history 
X 
Hepatitis screen 
X 
Urinalysis sample 
X 
X 
X 
X 
X 
EQ-5D and DMDSAT 
X 
X 
X 
X 
X 
X 
X 
X 
Provided to subject at Visit 1 for at-home completion 
between visits and reviewed for compliance in clinic 
DMD Upper Limb PROM 
X 
X 
X 
X 
X 
X 
X 
Performed only in subjects ≥7 years at baseline 
Height 
X 
X 
X 
X 
X 
X 
X 
X 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
X 
X 
X 
X 
Full (Visit 1, 8) or symptom-directed (Visit 2, 4, 6) 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
Genotyping sample 
X 
Hematology sample 
X 
X 
X 
X 
X 
Biochemistry sample 
X 
X 
X 
X 
X 
To be collected in fasted state (except Visit 1) 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
Myometry 
X 
X 
X 
X 
X 
X 
X 
X 
Performed only in subjects <7 years at baseline 
PUL 
X 
X 
X 
X 
X 
X 
X 
X 
Performed only in subjects ≥7 years at baseline 
6-minute walk test (1st test) 
X 
X 
X 
X 
X 
X 
X 
X 
6-minute walk test (2nd test) 
X 
X 
NSAA 
X 
X 
X 
X 
X 
X 
X 
X 
Timed function tests 
X 
X 
X 
X 
X 
X 
X 
X 
Study drug dispensed 
X 
X 
X 
X 
X 
X 
X 
Open-label study drug dispensed at Visit 8 
Study drug compliance 
X 
X 
X 
X 
X 
X 
12-lead ECG 
X 
X 
X 
X 
Spirometry 
X 
X 
X 
Required at all visits after subject loses ambulation 
Echocardiogram 
X 
X 
Randomization 
X 
Access IRT system to randomize subject 
Upper leg imaging 
X 
X 
X 
X 
Performed only at pre-qualified sites. May be done 
between Visits 1 and 2 (pre-treatment assessment) or 
±4 weeks of visit (post-treatment assessments). 
Abbreviations: DMD = Duchenne Muscular Dystrophy, DMDSAT = DMD Functional Ability Self-Assessment Tool, ECG = electrocardiogram, EQ-5D = EuroQoL 
5-Dimension, IRT = interactive response technology, NSAA = North Star Ambulatory Assessment, PROM = Patient-Reported Outcome Measure, PUL = 
Performance of Upper Limb 

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Table 4. 
Schedule of Events (Open-Label Treatment Period) 
 
 
 
 
 
 
 
Urinalysis 
X 
X 
X 
EQ-5D and DMDSAT 
X 
X 
X 
Provided to subject at Visit 1 for at-home completion 
between visits and reviewed for compliance in clinic 
DMD Upper Limb PROM 
X 
X 
X 
Performed only in subjects ≥7 years old at baseline 
Height 
X 
X 
X 
Weight 
X 
X 
X 
Physical examination 
X 
Full (Visit 11) 
Concomitant medications 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
Hematology sample 
X 
X 
X 
Biochemistry sample 
X 
X 
X 
To be collected in fasted state 
PK sample 
X 
Pre-morning dose and 2 hours post-morning dose 
Vital signs 
X 
X 
X 
PUL 
X 
X 
X 
Performed only in subjects ≥7 years old at baseline 
Myometry 
X 
X 
X 
Performed only in subjects <7 years old at baseline 
6-minute walk test 
X 
X 
X 
NSAA 
X 
X 
X 
Timed function tests 
X 
X 
X 
Study drug dispensed 
X 
X 
Open-label study drug dispensed at Visit 8 
Study drug compliance 
X 
X 
X 
12-lead ECG 
X 
Spirometry 
X 
Required at all visits after subject loses ambulation 
Echocardiogram 
X 
Upper leg imaging 
X 
Performed only at pre-qualified sites. May be 
assessed ±4 weeks of visit date 
Abbreviations: DMD = Duchenne muscular dystrophy, DMDSAT = DMD Functional Ability Self-Assessment Tool, ECG = electrocardiogram, EQ-5D = 
EuroQoL 5-Dimension, NSAA = North Star Ambulatory Assessment, PK = pharmacokinetic; PROM = Patient-Reported Outcome Measure, PUL = Performance 
of Upper Limb 
Study Period 
Open-Label Treatment 
Follow-Up 
Notes 
Study Week 
96 
120 
144 
148 
Visit Window (days) 
±7 
±7 
±7 
±7 
Visit Number 
9 
10 
11 
12 (by phone) 
Subjects who discontinue prematurely should 
complete Visit 11 and Visit 12 (by phone). Post 
treatment follow-up is not required if subjects are 
transitioning to another ataluren clinical trial. 

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6.2 
Explanation of Study Procedures 
6.2.1 
Pretreatment, Treatment, and Follow-Up Periods 
No study-related procedures should be performed prior to the signature of the informed 
consent/assent document(s). To accommodate subjects who must travel a long distance to 
visit the site, a subject may be consented by phone prior to Visit 1 if this is allowed by local 
regulation; in this situation, the screening period of up to 2 weeks will begin on the date of 
Visit 1. After a subject has completed the necessary screening assessments and has been 
confirmed to be eligible by the investigator, the baseline visit (Visit 2) for the subject can be 
scheduled. 
To the extent possible, excessive physical activity should be avoided on the day prior to a 
clinic visit; if the subject will be undergoing MRI, then excessive physical activity should be 
avoided for 3 days prior to the imaging procedure. All clinic visits should occur in the 
morning, at approximately the same time of day throughout the study. Ideally, the 
procedures should be performed in the same sequence at each visit. A recommended 
sequence of procedures is provided in the Study Reference Manual; however, feedback from 
the parent/caregiver may be considered in determining whether an alternative sequence may 
be more appropriate for an individual subject based on factors such as attention span, anxiety 
about blood tests, etc. For subjects on an intermittent treatment regimen of a corticosteroid, 
clinic visits ideally should be scheduled such that study-related evaluations are performed at 
the same approximate timepoint within a subject’s corticosteroid regimen in order to avoid 
confounding effects due to the corticosteroids. 
6.2.1.1 
Screening Period 
Following signature of the informed consent/assent document(s), subjects will report to the 
clinic for the performance of screening procedures (Visit 1) as noted in Table 3. The 
screening period is up to 2 weeks in duration; if necessary to schedule the baseline MRI 
(Section 6.2.26), the screening period may be extended by up to 1 additional week. 
Following the completion of these procedures, availability of the corresponding procedure 
results, and successful completion of the Screening entry to the electronic data capture 
(EDC)/IRT system, eligible subjects will return to the clinic for the performance of baseline 
procedures (Visit 2). 
6.2.1.2 
Baseline Treatment Visit (Visit 2) 
Before initiating treatment, each study participant will report to the clinic no later than the 
morning of Day 1 (Visit 2). Fasting for at least 8 hours prior to blood collection is required. 
On Day 1, the DMD Upper Limb PROM should be administered (if the subject is ≥7 years 
old) prior to the performance of the other study-related procedures. The subject will return to 
the clinic the next day for the 2nd 6MWT. After the completion of the 2nd baseline 6MWT 
(Day 2), the investigator must confirm eligibility. Following investigator confirmation of 
eligibility, a site representative should access the IRT system and supply the necessary 
information to obtain a subject randomization number and treatment assignment 
(see Section 4.3). Study drug will be dispensed on Day 2 of the baseline visit and the subject 

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and/or parent/caregiver will be instructed regarding study drug storage, reconstitution, and 
administration. The subject will remain at the clinic until released by the investigator. 
6.2.1.3 
Treatment Visits During Study 
Each subject will subsequently return to the clinical research facility at Week 12 (Visit 3) 
Week 24 (Visit 4), Week 36 (Visit 5), Week 48 (Visit 6), Week 60 (Visit 7), Week 72 
(Visit 8), Week 96 (Visit 9), and Week 120 (Visit 10). Fasting for at least 8 hours prior to 
blood collection is required; blood collection will be performed at Week 24 (Visit 4), 
Week 48 (Visit 6), Week 72 (Visit 8), Week 96 (Visit 9), and Week 120 (Visit 10). At these 
visits, the DMD Upper Limb PROM should be administered (if the subject is ≥7 years old) 
prior to the performance of the other study-related procedures. 
Because of potential changes in subject body weight over time, at Week 24 (Visit 4), 
Week 48 (Visit 6), Week 72 (Visit 8), Week 96 (Visit 9), and Week 120 (Visit 10), a dose 
adjustment may be made based on the subject’s body weight at that visit. Depending upon 
the magnitude of change in subject body weight since baseline, the number and strengths of 
sachets to be used by the subject may remain the same or may be adjusted. If the dose is 
adjusted, then the new IRT system-determined dose will be initiated on the morning 
immediately after the applicable visit. 
6.2.1.4 
End of Treatment 
The subject will return to the clinical research facility at Week 144 (Visit 11) for the 
End-of-Treatment Visit. If the subject discontinues prematurely (ie, before Week 144) and 
the last visit to the investigational site occurred >3 weeks previously, the procedures that 
would normally be performed at Week 144 should be performed as a Premature- 
Discontinuation Visit before the subject leaves the study. Fasting for at least 8 hours prior to 
blood collection is required. The DMD Upper Limb PROM should be administered (if the 
subject is ≥7 years old) prior to the performance of the other study-related procedures. 
6.2.1.5 
Post-Treatment Follow-Up Phone Visit 
The subject will be contacted by phone 4 weeks (±7 days) after the last dose of study drug for 
assessment of AEs and concomitant medications. If the End-of-Treatment Visit occurs 
>4 weeks after the last dose of study drug, the Post-Treatment Follow-Up Phone Visit does 
not need to be performed. Post-treatment follow-up s not required for subjects who will 
continue to receive post-study access to ataluren. 
6.2.2 
Informed Consent 
The investigator, or a sub-investigator listed on the Statement of Investigator Form Food and 
Drug Administration (FDA) 1572, must inform each prospective subject of the nature of the 
study, explain the potential risks, and obtain written informed consent/assent from the subject 
and/or the parent/legal guardian prior to performing any study related- screening procedures. 
Subjects will be re-consented with the appropriate age related-documents as needed, if 
required by local regulations. 

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6.2.3 
Clinical/Medication History 
The investigator should review the subject’s clinical history, including details relating to 
DMD and any other medical conditions. Information regarding current medications must be 
captured on the concomitant medication CRF. Details regarding corticosteroid use within 
12 months prior to study entry will be collected on a specific CRF. 
6.2.4 
Hepatitis Screen 
Tests include hepatitis A antibody, hepatitis B core antibody, and hepatitis C antibody. The 
Central Laboratory Manual should be consulted for collection, processing, and shipping 
details. Note: Only hepatitis B and C results are required for eligibility determination. 
6.2.5 
Vital Signs 
Vital signs (including systolic and diastolic blood pressure, pulse rate, and body temperature) 
will be monitored at Screening (Visit 1), baseline (Visit 2), Week 12 (Visit 3) Week 24 
(Visit 4), Week 36 (Visit 5), Week 48 (Visit 6), Week 60 (Visit 7), Week 72 (Visit 8), 
Week 96 (Visit 9), Week 120 (Visit 10), and Week 144 (Visit 11 - End of Treatment/ 
Premature Discontinuation). The pulse rate and blood pressure determinations will be 
performed with the subject in a sitting position after a 5-minute rest. Blood pressure will be 
measured in triplicate and the average will be recorded, as described in the study reference 
manual. 
6.2.6 
Height, Weight, and Physical Examination 
Height (in cm) and weight (in kg) will be measured at Screening (Visit 1), Baseline (Visit 2), 
Week 12 (Visit 3), Week 24 (Visit 4), Week 36 (Visit 5), Week 48 (Visit 6), Week 60 
(Visit 7), Week 72 (Visit 8), Week 96 (Visit 9), Week 120 (Visit 10), and Week 144 (Visit 11 
- End of Treatment/Premature Discontinuation). If the subject is unable to stand, sitting arm 
span and ulna length should be assessed as surrogate measurements for height. 
A full physical examination (including evaluation of cardiovascular system, chest and lungs, 
thyroid, abdomen, nervous system, skin and mucosae, musculoskeletal system, eyes, ears, 
nose, mouth, throat, spine, lymph nodes, extremities, and genitourinary) will be conducted at 
Screening (Visit 1), Week 72 (Visit 8), and Week 144 (Visit 11 - End of 
Treatment/Premature Discontinuation). 
A symptom-directed physical examination will be conducted at Baseline (Visit 2), Week 24 
(Visit 4), and Week 48 (Visit 6). 
Physical examinations may also be performed at any time during the study as clinically 
indicated. 
6.2.7 
Genotyping 
Blood for genotyping of genetic modifier candidates (latent TGF-beta binding protein 4 
[LTBP4], secreted phosphoprotein 1 [SPP1], cluster of differentiation 40 [CD40]) and 
thrombospondin 1 [TBHS1] will be collected at Baseline (Visit 2). Sequencing of the 
dystrophin gene to confirm the presence of a nonsense mutation also will be performed. This 
sample will be stored at the central laboratory. This blood sample will be destroyed after the 

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test is completed and a final report is generated by the designated central laboratory. The 
Study Manual should be consulted for collection, processing, and shipping details. 
6.2.8 
Hematology Laboratory Assessment 
Hematology laboratory assessments will include white blood cell count with differential, 
hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean 
corpuscular hemoglobin concentration, total red cell count with morphology, and platelet 
count. These parameters will be measured at Screening (Visit 1), baseline (Visit 2), Week 24 
(Visit 4), Week 48 (Visit 6), Week 72 (Visit 8), Week 96 (Visit 9), Week 120 (Visit 10), and 
Week 144 (Visit 11 - End of Treatment/Premature Discontinuation). Hematology parameters 
will be analyzed by the central laboratory. The Central Laboratory Manual should be 
consulted for collection, processing, and shipping details. 
6.2.9 
Serum Biochemistry Laboratory Assessment 
Biochemistry laboratory assessments will include sodium, potassium, chloride, bicarbonate, 
BUN, creatinine, magnesium, calcium, phosphorus, uric acid, glucose, total protein, albumin, 
globulin, albumin:globulin ratio, bilirubin (direct and indirect), AST, ALT, GGT, CK, lactate 
dehydrogenase (LDH), alkaline phosphatase, total cholesterol, high-density lipoprotein 
(HDL), low-density lipoprotein (LDL), triglycerides, and cystatin C. These parameters will 
be measured at Screening (Visit 1), Baseline (Visit 2), Week 24 (Visit 4), Week 48 (Visit 6), 
Week 72 (Visit 8), Week 96 (Visit 9), Week 120 (Visit 10), and Week 144 (Visit 11 - End of 
Treatment/Premature Discontinuation). Subjects should have fasted for at least 8 hours prior 
to blood collection; this is not necessary at screening (Visit 1). Biochemistry parameters will 
be analyzed by the central laboratory. The Central Laboratory Manual should be consulted 
for collection, processing, and shipping details. 
6.2.10 
Pharmacokinetic Assessment 
Ataluren concentrations in PK samples will be determined using a validated LC-MS/MS 
method. The Central Laboratory Manual should be consulted for timing of collection, 
processing, and shipping details. 
6.2.11 
Urinalysis 
Urinalysis will include analysis for pH, specific gravity, glucose, ketones, blood, protein, 
urobilinogen, bilirubin, nitrite, and leukocytes. These parameters will be measured at 
Screening (Visit 1), Baseline (Visit 2), Week 24 (Visit 4), Week 48 (Visit 6), Week 72 
(Visit 8), Week 96 (Visit 9), Week 120 (Visit 10), and Week 144 (Visit 11 - End of 
Treatment/Premature Discontinuation). These parameters will be analyzed by the central 
laboratory. Urine samples will also be collected and shipped to central laboratory for 
assessment of urine protein, creatinine, osmolality, and urinalysis. The Central Laboratory 
Manual should be consulted for collection, processing, and shipping details. 

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6.2.12 
12-Lead ECG 
A 12-lead ECG will be obtained at Screening (Visit 1), Week 24 (Visit 4), Week 48 (Visit 6), 
Week 72 (Visit 8), and Week 144 (Visit 11 - End of Treatment/Premature Discontinuation). 
The ECG will be performed and interpreted locally. The findings will be captured in source 
documents and with the CRF. 
A follow-up ECG may also be performed at any time during the study as clinically indicated 
at the discretion of the investigator. The PTC medical monitor must be informed via e-mail 
that an additional ECG was obtained and the SAE reporting process should be followed, if 
applicable. 
6.2.13 
Spirometry 
Spirometric evaluation of FVC and other parameters (eg, maximal inspiratory and expiratory 
pressures, peak expiratory flow) in the sitting position will be performed at screening 
(Visit 1), Baseline (Visit 2), Week 72 (Visit 8), and Week 144 (Visit 11 - End of 
Treatment/Premature Discontinuation). If a patient loses ambulation as determined by 
inability to perform the 10-meter run/walk test within 30 seconds at a clinic visit, then 
spirometry will be performed at that visit and at all subsequent visits. 
6.2.14 
Echocardiogram 
An echocardiogram will be obtained at Screening (Visit 1), Week 72 (Visit 8), and Week 144 
(Visit 11 – End of Treatment/Premature Discontinuation). 
6.2.15 
Study Drug Randomization 
After the completion of the 2nd baseline 6MWT at Week 1, Day 2 (Visit 2, Day 2), a site 
representative should access the IRT system, following investigator confirmation of 
eligibility and supply the necessary information to obtain a subject randomization number 
and treatment assignment (see Section 4.3) in anticipation of administration of the first dose 
of study drug on the morning or afternoon on Day 2 of the Baseline visit (Visit 2, Day 2). If 
there is a delay in starting of study drug administration, all subsequent visits will be timed 
relative to the date that dosing is initiated. 
6.2.16 
Study Drug Administration 
Refer to Section 5.2. 
6.2.17 
Study Drug Compliance 
Subjects and/or parents/caregivers will return unused study drug (sachets and kits) to the 
study site for full compliance assessments. 

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6.2.18 
Adverse Events 
AEs must be assessed and documented at each clinic visit. This information will be collected 
at Screening (Visit 1), Baseline (Visit 2), Week 12 (Visit 3) Week 24 (Visit 4), Week 36 
(Visit 5), Week 48 (Visit 6), Week 60 (Visit 7), Week 72 (Visit 8), Week 96 (Visit 9), 
Week 120 (Visit 10), and Week 144 (Visit 11 - End of Treatment/Premature 
Discontinuation). AEs also will be assessed during the Post-Treatment Follow-Up Phone 
Call (4 weeks post discontinuation of study drug). In addition, subjects and 
patients/caregivers will be encouraged to report AEs of concern at any time in the intervals 
between visits. 
6.2.19 
Concomitant Medications 
Information regarding any concomitant medications administered, as well as information 
regarding all non-drug therapies, will be collected throughout the study. This information 
will be collected at Screening (Visit 1), Baseline (Visit 2), Week 12 (Visit 3) Week 24 
(Visit 4), Week 36 (Visit 5), Week 48 (Visit 6), Week 60 (Visit 7), Week 72 (Visit 8), 
Week 96 (Visit 9), Week 120 (Visit 10), and Week 144 (Visit 11 - End of Treatment/ 
Premature Discontinuation). Concomitant medication information also will be collected 
during the Post-Treatment Follow-Up Phone Call (4 weeks post discontinuation of study 
drug). 
6.2.20 
Myometry 
Myometry will be performed only in subjects who are <7 years old at baseline. 
Upper and lower extremity myometry will be performed using a myometer following 
standardized procedures (see Study Manual for detailed instructions). Muscle groups to be 
evaluated include knee extensors and elbow flexors. Bilateral assessments should be done 
and 3 measurements should be recorded from each muscle group on each side if possible. 
These parameters will be monitored at screening (Visit 1), Baseline (Visit 2), Week 12 
(Visit 3) Week 24 (Visit 4), Week 36 (Visit 5), Week 48 (Visit 6), Week 60 (Visit 7), 
Week 72 (Visit 8), Week 96 (Visit 9), Week 120 (Visit 10), and Week 144 (Visit 11 - End of 
Treatment/Premature Discontinuation). 
6.2.21 
Performance of Upper Limb 
PUL will be assessed only in subjects who are ≥7 years old at baseline. 
PUL will be administered using standardized equipment and procedures (see Study Manual 
for detailed instructions) at screening (Visit 1), Baseline (Visit 2), Week 12 (Visit 3) 
Week 24 (Visit 4), Week 36 (Visit 5), Week 48 (Visit 6), Week 60 (Visit 7), Week 72 
(Visit 8), Week 96 (Visit 9), Week 120 (Visit 10), and Week 144 (Visit 11 - End of 
Treatment/Premature Discontinuation). 

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6.2.22 
6-Minute Walk Test 
Ambulation and endurance will be assessed via the 6MWT following standardized 
procedures (see Study Manual for detailed instructions). The 6MWT will be performed at 
Screening (Visit 1), Baseline (Visit 2, two 6MWTs performed), Week 12 (Visit 3) Week 24 
(Visit 4), Week 36 (Visit 5), Week 48 (Visit 6), Week 60 (Visit 7), Week 72 (Visit 8, two 
6MWTs performed), Week 96 (Visit 9), Week 120 (Visit 10), and Week 144 (Visit 11 - End 
of Treatment/Premature Discontinuation). 
6.2.23 
North Star Ambulatory Assessment 
The NSAA will be used to evaluate physical function, using standardized procedures 
(see Study Manual for detailed instructions). The NSAA will be performed at Screening 
(Visit 1), Baseline (Visit 2), Week 12 (Visit 3) Week 24 (Visit 4), Week 36 (Visit 5), 
Week 48 (Visit 6), Week 60 (Visit 7), Week 72 (Visit 8), Week 96 (Visit 9), Week 120 
(Visit 10), and Week 144 (Visit 11 - End of Treatment/Premature Discontinuation). 
6.2.24 
Timed Function Tests 
Timed function tests of peak physical capacity, including the times taken to climb 4 stairs, 
and descend 4 stairs, will be performed using standardized procedures (see Study Manual for 
detailed instructions). These assessments will be performed at Screening (Visit 1), Baseline 
(Visit 2), Week 12 (Visit 3) Week 24 (Visit 4), Week 36 (Visit 5), Week 48 (Visit 6), 
Week 60 (Visit 7), Week 72 (Visit 8), Week 96 (Visit 9), Week 120 (Visit 10), and 
Week 144 (Visit 11 - End of Treatment/Premature Discontinuation). 
Time to run/walk 10 meters and time to stand from supine will be assessed as part of the 
NSAA (Section 6.2.23). 
6.2.25 
DMD Upper Limb PROM 
DMD Upper Limb PROM will be assessed only in subjects who are ≥7 years old at baseline. 
The DMD Upper Limb PROM questionnaire will be available in all languages relevant for 
this study and will be completed by the parent/caregiver. If possible, the same 
parent/caregiver should complete the questionnaire each time. The DMD Upper Limb 
PROM questionnaire will be completed at Baseline (Visit 2), Week 12 (Visit 3) Week 24 
(Visit 4), Week 36 (Visit 5), Week 48 (Visit 6), Week 60 (Visit 7), Week 72 (Visit 8), 
Week 96 (Visit 9), Week 120 (Visit 10), Week 144 (Visit 11 - End of Treatment/Premature 
Discontinuation). Refer to the Study Manual for further details on how to administer the 
DMD Upper Limb PROM questionnaire. 
6.2.26 
Magnetic Resonance Imaging/Spectroscopy 
MRI and/or magnetic resonance spectroscopy (MRS) will be conducted at a subset of sites 
that have been pre-qualified by a central imaging vendor to perform this assessment. To be 
pre-qualified, a site must have access to a whole-body scanner and appropriate personnel at 
the site must have been trained on the procedure for data acquisition. A list of qualified sites 
and documentation of equipment and training, as well as whether the site is performing MRI 
only or MRI and MRS, will be maintained. MRI/MRS data will be analyzed centrally. 
MRI/MRS will be performed at Baseline (Visit 2), Week 24 (Visit 4), Week 48 (Visit 6), 

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Week 72 (Visit 8), and Week 144 (Visit 11 – End of Treatment/Premature Discontinuation). 
The baseline imaging may be performed during the screening period, and post-baseline 
imaging may be performed ±4 weeks of visit date. To the extent possible, excessive physical 
activity should be avoided for 3 days prior to imaging assessments. 
Subjects with a contraindication to imaging (eg, subjects with a fear of closed spaces or with 
metal objects in the body that are not scanner-safe) should not undergo imaging but can 
participate in the rest of the study. 
6.2.27 
At-Home Questionnaires 
HRQL will be measured using the EQ-5D and patient-reported functional ability will be 
measured using the DMD Self-Assessment Tool [Landfeldt 2015]. These questionnaires will 
only be completed where validated versions in the local language are available. The 
questionnaires will be completed by the subject (where possible) and a parent/caregiver. If 
possible, the same parent/caregiver should complete the questionnaire each time. The 
questionnaires will be provided at Visit 1 and completed at home by the subject and a 
parent/caregiver between Visit 1 and Visit 2 (pre-treatment) and approximately once per 
month for the rest of the study. Site personnel will assess subject compliance with the 
questionnaires at Baseline (Visit 2), Week 12 (Visit 3) Week 24 (Visit 4), Week 36 (Visit 5), 
Week 48 (Visit 6), Week 60 (Visit 7), Week 72 (Visit 8), Week 96 (Visit 9), Week 120 
(Visit 10), and Week 144 (Visit 11 - End of Treatment/Premature Discontinuation). Refer to 
the Study Manual for further details on the at-home questionnaires. 
6.3 
Blood Collection Summary 
Assuming a patient completes the study, the maximum amount of blood to be drawn at a visit 
is approximately 20 mL and the total amount of blood to be drawn over the entire study 
period is approximately 81 mL. 
7 
ADVERSE EVENT ASSESSMENTS 
7.1 
Adverse Event Definitions 
7.1.1 
Adverse Events 
An AE is any untoward medical occurrence associated with the use of a drug in humans, 
whether or not it is considered related to the drug. An AE can therefore be any unfavorable 
and unintended sign (including an abnormal laboratory finding), symptom, or disease in a 
study subject who is administered study drug in this study. 
For this protocol, untoward medical occurrences that should be reported as AEs include the 
following: 
● 
All AEs during the course of treatment with study drug administration. 
● 
All AEs resulting from medication misuse, abuse, withdrawal, or overdose, of 
study drug. 
● 
All AEs resulting from medication errors such as dispensing or administration 
error outside of what is described in the protocol. 

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● 
Worsening of a preexisting illness. 
● 
Injury or accidents. 
● 
Abnormalities in physiological testing or physical examination findings that 
require clinical intervention or further investigation (beyond ordering a repeat 
[confirmatory] test). 
● 
Laboratory or ECG abnormalities that require clinical intervention or further 
investigation (beyond ordering a repeat [confirmatory] test) unless they are 
associated with an already reported clinical event. Laboratory abnormalities 
associated with a clinical event should be captured in the source documents. 
Laboratory abnormalities not requiring clinical intervention or further 
investigation will be captured as part of overall laboratory monitoring, and should 
not be reported as AEs. 
● 
A preexisting condition (eg, allergic rhinitis) must be noted on the appropriate 
electronic CRF (eCRF) for Visit 1, but should not be reported as an AE unless the 
condition worsens or episodes increase in frequency during the AE reporting 
period. Diagnostic and therapeutic non-invasive and invasive procedures, such as 
surgery, should not be reported as AEs. However, the medical condition for which 
the procedure was performed should be reported if it meets the definition of an 
AE. For example, an acute appendicitis that occurs during the treatment with 
study drug should be reported as the AE and the resulting appendectomy should be 
recorded in the source documents and CRF. If a surgical procedure was planned 
prior to entry into the study, and the surgery is not performed because of a 
worsening of a baseline condition, this should not be reported as an AE. Note that, 
as described in Section 7.1.2, any inpatient hospitalization occurring as the 
consequence of an AE during the study period should be reported as an SAE. 
7.1.2 
Serious Adverse Events (SAEs) 
An AE that results in one of the following: 
● 
Results in death. This includes all deaths on treatment or within 4 weeks after last 
study drug administration, including deaths due to disease progression. Any death 
occurring later than 4 weeks following the last dose need not be reported as an 
SAE unless it is a result of an event that started within the period covered by the 
on-study definition. The reported AE should be the event that caused the death. 
● 
Is life-threatening. This refers to an event in which the subject was at risk of death 
at the time of the event. It does not include an event that, had it occurred in a more 
severe form, hypothetically might have caused death. 
● 
Requires inpatient hospitalization or prolongation of existing hospitalization 
(excluding hospitalizations for administration of the study drug, procedures 
required by the study protocol, or DMD-related diagnostic procedures; other 
planned hospitalizations; or hospitalizations related only to progression of 
disease). Treatments in the emergency room for procedures such as hydration that 
do not require admitting the subject to the hospital and observational durations in 
the emergency room for less than 24 hours do not fall into this category. 

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● 
Results in persistent or significant disability or incapacity or substantial disruption 
of the ability to conduct normal life functions, not related to DMD. 
● 
Important medical event: These are AEs that might not be immediately life- 
threatening or result in death or hospitalization but might jeopardize the subject or 
might require intervention to prevent one of the other outcomes listed above. 
Medical judgment should be exercised in deciding whether an AE is serious based 
on above definition. Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in inpatient hospitalization, or development of drug 
dependency or drug abuse. 
● 
A pregnancy resulting in spontaneous abortion, stillbirth, neonatal death, or 
congenital anomaly (including that in an aborted fetus). 
7.1.3 
Unexpected Adverse Events 
Unexpected AEs are events that are not consistent with the reference safety information 
(RSI) for the medicinal product, or the nature, severity, or outcome of which is not consistent 
with the expected events as per the RSI. For example, under this definition, hepatic necrosis 
would be unexpected (by virtue of greater severity) if the Investigator Brochure only referred 
to elevated hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and cerebral 
vasculitis would be unexpected (by virtue of greater specificity) if the Investigator Brochure 
only listed cerebral vascular accidents. 
For the purposes of considering expectedness, the Ataluren Investigator Brochure provides a 
section referred to as the Reference Safety Information. 
7.2 
Eliciting Adverse Event Information 
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject or parent/guardian in case of a child. In addition, each study subject will be 
questioned about AEs at each scheduled clinic visit after study drug administration or during 
any telephone contact with the subject or parent/guardian in case of a child. The type of 
question asked should be open-ended, eg-, “How has your child been feeling?” or a similar 
type of query. 
7.3 
Adverse Event Recording 
All AEs (both serious and nonserious) that occur in subjects during the AE reporting period 
must be recorded, whether or not the event is considered drug-related. 
All AEs are to be recorded in the source documents and on the eCRF using concise medical 
terminology; whenever possible terms contained in Medical Dictionary for Regulatory 
Activities (MedDRA) should be employed. In addition, the following information should be 
recorded: 
● 
Indication of whether the event is serious or nonserious (see Section 7.1.2) 
● 
Relationship to study drug (see Section 7.4) 
● 
Severity of the event (see Section 7.5) 

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● 
Onset date 
● 
Resolution date, or date of death 
● 
Action taken 
● 
Outcome of the event 
Classification of the event as serious or nonserious determines the reporting procedures to be 
followed. 
7.4 
Describing Adverse Event Relationship to Study Drug 
Based on the considerations outlined in Table 5, the investigator should provide an 
assessment of the relationship of the AE to the study drug, ie, whether there is a reasonable 
possibility that the study drug caused the AE. 
Table 5. 
Relationship of Study Drug to Adverse Event 
 
Relationship 
Description 
Probable 
A clinical event in which a relationship to the study drug seems probable because 
of such factors as consistency with known effects of the drug; a clear temporal 
association with the use of the drug; improvement upon withdrawal of the drug; 
recurrence upon rechallenge with the drug; lack of alternative explanations for the 
event. 
Possible 
A clinical event occurring coincident with administration of the study drug and 
which may or may not be explained by concurrent disease or other drugs or 
chemicals. Information on drug withdrawal or rechallenge may be lacking. 
Unlikely 
A clinical event with a temporal relationship to the study drug exposure that does 
not preclude causality but for which there is a clear alternate cause that is more 
likely to have caused the AE than study drug. Such alternatives include a 
concomitantly administered drug, the subject’s disease state, other medical 
conditions, or environmental factors. 
Unrelated 
A clinical event for which a relationship to the study drug seems improbable 
because of factors such as inconsistency with known effects of the study drug, lack 
of a temporal association with study drug administration, lack of association of the 
event with study drug withdrawal or rechallenge, and/or presence of alternative 
explanations for the event. Alternative explanations might include a known 
relationship of the AE to a concomitant drug, medical history of a similar event, the 
subject’s disease state, other medical conditions, or environmental factors. 
 
7.5 
Grading of Severity of Adverse Events 
The severity of AEs will be graded using the CTCAE Version 4.0. For each episode, the 
highest severity grade attained should be reported. 
If a CTCAE criterion does not exist, the investigator should use the grade or adjectives: 
Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or Grade 5 
(fatal) to describe the maximum intensity of the AE. For purposes of consistency with the 
CTCAE, these intensity grades are defined in Table 6. 

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Table 6. 
Grading of Adverse Event Severity 
 
Grade 
Adjective 
Description 
Grade 1 Mild 
Sign or symptom is present, but it is easily tolerated, is not expected to 
have a clinically significant effect on the subject’s overall health and well- 
being, does not interfere with the subject’s usual function, and is not likely 
to require medical attention 
Grade 2 Moderate 
Sign or symptom causes interference with usual activity or affects clinical 
status, and may require medical intervention 
Grade 3 Severe 
Sign or symptom is incapacitating or significantly affects clinical status and 
likely requires medical intervention and/or close follow-up 
Grade 4 Life-threatening Sign or symptom results in a potential threat to life 
Grade 5 Fatal 
Sign or symptom results in death 
Note the distinction between the seriousness and the severity of an AE. Severe is a measure 
of intensity; thus, a severe reaction is not necessarily a serious event. For example, a 
headache may be severe in intensity, but would not be classified as serious unless it met one 
of the criteria for serious events listed in Section 7.1.2. 
7.6 
Pregnancy of Female Partners 
PTC Therapeutics should be notified in the event that a female partner of a subject becomes 
pregnant at any time after the subject’s first dose of study drug. Any such pregnancy 
occurring on-study or within 30 days of the last administration of study drug must be 
reported on a Pregnancy Notification Form. This must be done whether or not an AE has 
occurred and within 24 hours of awareness of the pregnancy. The information submitted 
should include the anticipated date of birth or pregnancy termination. 
Written consent is required prior to collecting and reporting any information on a female 
partner of a subject. 
If possible, the investigator should follow the pregnant female partner of the subject until 
completion of the pregnancy and notify the PTC Therapeutics medical monitor and PTC 
Pharmacovigilance of the outcome within 24 hours. The investigator will provide this 
information as a follow--up to the initial Pregnancy Notification Form via the Pregnancy 
Outcome Form (see Study Manual for details). 
If the outcome of the pregnancy meets the criteria for immediate classification as an SAE 
(ie, spontaneous abortion, stillbirth, neonatal death, or congenital anomaly [including in an 
aborted fetus]), the investigator should follow the procedures for reporting SAEs, ie, report 
the event to the PTC Therapeutics Safety Department or designee and follow up by 
submission of appropriate AE CRFs (see Section 7.9). 

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7.7 
Follow-Up of Unresolved Adverse Events 
All AEs should be followed up by the investigator until they are resolved, or the investigator 
assesses them as chronic or stable. The investigator should consider protocol guidelines and 
use his/her discretion in ordering additional tests as necessary to monitor the resolution of 
such events. In the event of additional investigations, the PTC Therapeutics 
Pharmacovigilance Department or designee should be informed via email or fax. A subject 
withdrawn from the study because of an AE must be followed by the investigator until 
clinical recovery is complete and laboratory results have returned to normal, or until 
progression has been stabilized. Follow-up may need to continue after the subject has 
discontinued from the study, and additional investigations may be requested by the medical 
monitoring team. 
7.8 
Adverse Event Reporting Period 
The first day of AE reporting will coincide with the day the informed consent is signed. The 
AE reporting period for this study ends with the 4-week (± 7 days) Post-Treatment Visit, 
except as described in Section 7.7. In addition, SAEs occurring in a subject after the study 
period should be reported to the sponsor if the investigator becomes aware of them. 
7.9 
Investigator Site Adverse Event Reporting Requirements 
Classification of an event as serious or non-serious (see Section 7.1.2) determines the 
reporting procedures to be followed. Investigator site reporting requirements for AEs are 
summarized in Table 7. 
Table 7. 
Investigator Site Reporting Requirements for Adverse Events 
 
Event 
Recorded on the eCRF 
Reported on the SAE/Pregnancy 
Report Form to PTC 
Pharmacovigilance Within 24 Hours 
of Awareness 
Serious AE 
All 
All 
Non-Serious AE 
All 
None 
Other, eg, paternal 
exposure before/during 
pregnancy, or occupational 
exposure 
All (regardless of whether 
associated with an AE), 
except occupational 
exposure 
All (regardless of whether associated 
with an AE) 
Abbreviations: AE, adverse event; eCRF, electronic case report form; SAE, serious adverse event 
 
7.10 
Serious Adverse Event Reporting 
All SAEs should be reported via the SAE report form to PTC Therapeutics within 24 hours 
of becoming aware of the event(s). In addition, the AE portion of the eCRF must also be 
completed. 
The SAE report form should be signed by the investigator; however, if the investigator is 
unable to sign at the time of the event or within 24 hours, the form should be signed by the 
clinical staff member reporting the SAE (eg, the study coordinator). The SAE report form 
must be faxed or emailed to the PTC Therapeutics Pharmacovigilance Department or 
designee and to the site IRB/EC (if required by local regulations) within 24 hours. Follow-up 
information to the SAE should be clearly documented as “follow-up” in the SAE report form 
and must also be faxed or emailed to the same party. All follow-up SAE report forms for the 

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event must be signed by the investigator. Any source documents (eg, progress notes, nurses’ 
notes, laboratory and diagnostic test results, discharge summaries) provided to the sponsor 
should be redacted so that the subject’s name, address, and other personal identity 
information are obscured. Only the subject’s study number and initials are to be provided 
(in regions where the provision of such information is permitted). The information in the AE 
portion of the CRF and the SAE report form(s) must match or be reconciled. Where the 
same data are collected, the forms must be completed in a consistent manner. For example, 
the same AE term should be used on both forms. 
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (for example, if a subject initially seeks treatment elsewhere), the investigator is 
to report the event within 24 hours after learning of it and to document his/her first awareness 
of the AE. 
The PTC Therapeutics Pharmacovigilance Department contact information for reporting 
SAEs is provided below. This information is also provided in the Study Manual and in the 
SAE report form. In Japan only, send to both email addresses. 
E-mail: 
Pharmacovigilance@ptcbio.com 
prj-as-ptc124-pv@eps.co.jp 
SAE Fax Line: 
1-908-325-0355 
7.11 
PTC Therapeutics Adverse Event Reporting Requirements 
As the sponsor of the study, PTC Therapeutics is responsible for reporting certain safety 
information, particularly SAEs and subject deaths related to participation in the study, to 
each investigator in an expedited manner. If notification of an AE requiring expedited 
reporting to investigators is received, PTC Therapeutics or its designated representative will 
contact each investigator site participating in this study by e-mail, fax, and/or overnight mail 
such that the investigator can promptly notify the site IRB/EC per their local requirements. 
The initial expedited safety report will be provided as required according to local regulations 
(eg, within 15 days) after the earliest date PTC Therapeutics or an agent of PTC Therapeutics 
(eg, a site monitor) becomes aware of an AE. This awareness date is the date the regulatory 
reporting clock begins and the date is considered Day 0. 

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8 
WITHDRAWAL OF SUBJECTS 
All subjects who receive study drug should remain in the study whenever possible, including 
after loss of ambulation. However: 
● 
The subject has the right to withdraw consent and discontinue study drug at any 
time. 
● 
If the subject’s condition substantially worsens after initiating study drug, the 
subject will be carefully evaluated by the investigator in consultation with the PTC 
Therapeutics medical monitor. The subject will be withdrawn from treatment if 
continuing would place them at risk. 
● 
Upon consultation with the PTC Therapeutics medical monitor, the investigator 
may withdraw the subject from study drug, if, in the investigator’s clinical 
judgment, it is not in the subject’s best interest to continue. 
● 
If the subject becomes significantly noncompliant with study drug administration, 
study procedures, or study requirements. In this event, the subject should be 
withdrawn from study treatment when the circumstances surrounding 
noncompliance increase risk to the subject or are anticipated to substantially 
compromise the interpretation of study results. 
● 
The subject will be withdrawn from treatment if he is unable to tolerate study drug. 
● 
The subject may be withdrawn from this study in circumstances where the blind is 
intentionally or accidentally broken. 
● 
This study may be discontinued by the relevant regulatory authority and/or PTC 
Therapeutics at any time. 
The date study drug is discontinued and the reason for discontinuation will be recorded in the 
source documents and in the eCRF. 
When study drug is discontinued (regardless of the reason), the investigator should 
encourage that all of the evaluations required at the End of Treatment Visit be performed and 
that any additional evaluations be completed that may be necessary to ensure that the subject 
is free of untoward effects. The subject should be encouraged to seek appropriate follow-up 
for any continuing health problems. 
Subjects may be replaced if they withdraw from the study because ataluren has become 
commercially available in their country. Subjects removed from the study for any other 
reason will not be replaced. 
9 
STATISTICS AND DATA MANAGEMENT 
Statistical considerations for this international study are described below. Any 
country-specific statistical considerations, if requested by regulatory authorities, will be 
described in a separate statistical analysis plan. 

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9.2 
Study Population Definition 
9.2.1 
Intention-to-Treat (ITT) Population 
This population will include all subjects who are randomized, with treatment assignments 
designated according to initial randomization, regardless of whether subjects receive a 
different study treatment from the one randomized. In addition, subjects in this population 
must have a valid 6MWT at baseline, and at least one valid post-baseline 6MWT. This 
population will be used for summary and analysis of efficacy endpoints. 
9.2.2 
Modified Intention-to-Treat (mITT) Population 
This population will include all subjects in the ITT population who meet the following 
additional criteria: ≥7 to ≤16 years old with 6MWD ≥300 meters and time to stand from 
supine ≥5 seconds at baseline. This population will be used for the primary endpoint 
analysis, and other supportive analyses. 
9.2.3 
As Treated - Population 
The as-treated population consists of all randomized subjects who receive study treatment, 
with treatment assignments designated according to actual treatment received. This 
population will be used for summary and analysis of safety endpoints. 
9.2.4 
Per-Protocol Population 
This population will include all subjects in the mITT population who meet the following 
additional criteria: received study treatment in agreement with randomization, completed the 
72-week double-blind treatment period, had drug compliance between 75% and 125%, 
inclusive, and had no inclusion or exclusion criteria violations and no major protocol 
violations. This population will be used for supportive efficacy analyses. 

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9.2.5 
Evaluable Populations 
In general, evaluable populations consist of all as-treated subjects who have sufficient data to 
assess the measure of interest (eg, HRQL questionnaire). These populations may be 
evaluated in the analysis of other secondary endpoints. 
9.3 
General Statistical Considerations 
By-subject listings will be created for each CRF module. Summary tables for continuous 
variables will contain the following statistics: n, mean, standard deviation, standard error, 
95% confidence intervals (CIs) on the mean, median, minimum, and maximum. Summary 
tables for categorical variables will include N (population), n (subgroup), percentage, and 
95% CIs on the percentage. Where applicable, the summary data (mean, standard error) will 
be presented in graphical form against time of visit. Unless otherwise specified, all 
inferential analyses will be 2-sided at the alpha (α) 0.05 level of significance. 
9.4 
Specific Statistical Analyses 
9.4.1 
Study Conduct and Subject Disposition 
The number of subjects screened and randomized, and the number of subjects completing all 
planned study assessments, will be summarized by treatment. Subjects who discontinue 
study drug or are removed from the study prematurely will be summarized by reason for 
discontinuation and treatment. Randomization errors, and timing of withdrawal from the 
study will be described. 
9.4.2 
Baseline Characteristics and Treatment Group Comparability 
Baseline subject characteristics for each study population, and for each phase of the study, 
will be summarized using frequency tables for categorical variables and descriptive statistics 
for quantitative variables. 
9.4.3 
Use of Concomitant Medication and Supportive Therapy 
Concomitant medications will be coded using the World Health Organization Drug 
Dictionary (WHODRUG), using Anatomical Therapeutic Chemical classification (ATC) 
codes. The incidence of specific concomitant medications will be summarized by treatment 
group, for the pre-treatment, double-blind, and open-label periods. Specific attention will be 
given to corticosteroids, and to drugs for prophylaxis and/or treatment of congestive heart 
failure. The type and timing (pre-treatment, double-blind, and open-label) of such drugs will 
be summarized by treatment group. The incidence of changes in regimen for such drugs will 
also be summarized for the double-blind and open-label periods. 

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9.4.5 
Secondary Endpoints 
9.4.5.1 
Timed Function Tests 
Timed function tests (10-meter run/walk, 4-stair stair-climb, and 4-stair stair descend) will be 
analyzed using the analysis methods outlined for the primary efficacy variable (MMRM and 
ANCOVA), for both the mITT and ITT populations, at the end of the double-blind and 
open-label phases. A separate analysis will evaluate 10-meter run/walk results in subjects 
with a baseline 6MWD <300 meters. An additional analysis will evaluate a composite 
endpoint of average change in times to run/walk 10 meters, climb 4 stairs, and descend 

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4 stairs. Subjects who cannot perform a timed function test within 30 seconds will be 
assigned a value of 30 seconds for the analysis. 
9.4.5.3 
North Star Ambulatory Assessment 
The NSAA consists of 17 activities, each scored as 0, 1, or 2. The sum of these 17 scores 
will be used to form a total score. This total score will be analyzed using the ANCOVA 
analysis method outlined for the primary efficacy variable, for both the mITT and ITT 
populations, at the end of the double-blind and open-label phases. A separate analysis for the 
open-label phase will evaluate changes in total score in subjects with a baseline 6MWD 
≥400 meters and <7 years of age. Transformation of the total score to a linear scale 
[Mayhew 2013a] also will be performed. In addition, the odds of losing one or more of the 
NSAA items (score of 1 or 2 at baseline transitioning to a 0 score post-baseline) will be 
evaluated for ataluren versus placebo subjects using a risk ratio derived via re-sampling 
based analysis methods; the “lifts head” item will be excluded from this analysis because it 
does not fit the original construct of the NSAA based on Rasch analysis [Mayhew 2013a]. 

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9.4.7 
Safety 
Vital sign results, including height and weight, will be summarized by treatment group, and 
by double-blind and open-label phases. Physical examination results will be listed. AEs will 
be classified using MedDRA, according to system organ class and preferred term. The 
severity of AEs will be graded according to the latest version of the CTCAE whenever 
possible. A treatment-emergent adverse event (TEAE) is defined as an AE that occurs or 
worsens in the period extending from the first dose of study drug to 4 weeks after the last 
dose of study drug in this study. The incidence of subjects experiencing specific TEAEs will 
be tabulated by treatment group, and by double-blind and open-label phases. Subjects 
experiencing the same event more than once will be counted only once. AEs will be 
summarized by worst CTCAE grade. AEs classified as CTCAE Grade 3 or higher, study- 
drug-related events, renal events leading to special diagnostic evaluations, events leading to 
discontinuation from treatment, and SAEs will be considered with special attention. 
Hematological data, serum biochemistry, and urine data will be summarized by treatment 
group, and by double-blind and open-label phases. Values will be graded according to 
CTCAE severity grade, when applicable. For variables graded according to CTCAE severity 
grade, the incidence of the worst severity grade observed will be displayed. For parameters 
for which a CTCAE scale does not exist, the frequency of subjects with values below, within, 
and above the normal ranges will be summarized by treatment group, and by double-blind 
and open-label phases. ECG data will be summarized by treatment group, and by double- 
blind and open-label phases. 
9.4.8 
Pharmacokinetic analyses 
Plasma concentration collected at the last visit (Week 144) will be summarized with 
descriptive statistics (eg, n, arithmetic mean, standard deviation, standard error, median, 
minimum, and maximum, CV% mean, geometric mean, and CV% geometric mean). 
Additionally, the SAP will be developed to include evaluation of correlation between 
plasmatic concentrations of ataluren and 6MWD and TFT, including time to run/walk 
10 meters, time to 10% worsening in 6MWD and other outcomes that are sufficiently 
sensitive. 
9.5 
Description and Timing of Analysis 
When all subjects have completed the study and data entry is complete, the database will be 
locked, archived, unblinded, and analyzed. 

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10 
OBLIGATIONS OF THE INVESTIGATOR AND THE SPONSOR 
10.1 
Compliance with Ethical and Regulatory Guidelines 
The investigator is responsible for ensuring that the clinical study is performed in accordance 
with the Declaration of Helsinki and the International Council for Harmonisation (ICH) GCP 
guidelines. 
10.2 
Institutional Review Board/Independent Ethics Committee 
Prior to enrollment of subjects into the study, as required by regulatory authorities, the 
protocol and informed consent document will be reviewed and approved by an appropriate 
IRB/EC. By signing the protocol, the investigator assures that approval of the protocol will 
be obtained from the IRB/EC and that all aspects of the IRB/EC review will be conducted in 
accordance with current regulations. Amendments to the protocol will be subject to the same 
IRB/EC review requirements as the original protocol. Only changes necessary to eliminate 
apparent immediate hazards to the subjects may be initiated prior to IRB/EC approval. In 
that event, the investigator must notify the IRB/EC and PTC Therapeutics in writing within 
the timeframe defined by local regulations. The investigator will also promptly notify the 
IRB/EC of any serious, unexpected AEs, or any other information that may affect the safe 
use of the drug during the course of the study. 
A letter documenting the IRB/EC approval and a list of the names and titles of the IRB/EC 
members must be received by PTC Therapeutics prior to the initiation of the study. All 
correspondence with the IRB/EC should be retained in the investigator’s study file. 
The investigator shall submit a progress report, at least once yearly, to the IRB/EC, and must 
provide a copy to PTC Therapeutics. As soon as possible after completion or termination of 
the study, the investigator will submit a final report to the IRB/EC and to PTC Therapeutics. 
This report should include the dates of initiation and completion of the study, a description of 
any changes in study procedures or amendments to the protocol, any deviations from the 
protocol, the number and type of subjects evaluated, the number of subjects who 
discontinued (and the reasons for discontinuation), the number of subjects who completed the 
study, and the results of the study, including a description of any AEs. PTC Therapeutics 
will assist the investigator in the preparation of this report, as needed. 
10.3 
Informed Consent/Assent 
By signing the protocol, the investigator assures that informed consent/assent will be 
obtained from each subject and/or parent/legal guardian prior to performing any study-related 
activities and that the informed consent/assent will be obtained in accordance with current 
regulations. 
The investigator, or a sub-investigator listed on the Statement of Investigator Form FDA 
1572, will give each subject and/or parent/guardian full and adequate verbal and written 
information regarding the objectives and procedures of the study and the possible risks 
involved. An informed consent/assent document will be provided to each subject and/or 
parent/guardian in a language in which the subject or parent/guardian is fluent. This 
information must be provided to the subject or parent/guardian prior to undertaking any 
studyrelated- procedure. Adequate time should be provided for the subject and/or 

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parent/guardian to read the informed consent, to understand the risks and benefits of 
participating in the study, and to ask any questions that the subject and/or parent/guardian 
may have about the study. The subject and/or parent/guardian should be able to ask 
additional questions as and when needed during the conduct of the study. The subject’s 
and/or parent(s)/guardian signature (as required by local regulations) on the informed consent 
form should be obtained at the investigator site in the presence of the investigator or a 
qualified representative (eg, sub-investigator). Where applicable, the subject will sign an 
age-appropriate assent form. 
Each subject or parent/guardian will be given a copy of the signed consent/assent form. The 
original signed informed consent forms will be retained by the investigator with the study 
records. 
The written subject information must not be changed without prior approval by PTC 
Therapeutics and the IRB/EC. 
10.4 
Electronic Case Report Forms 
An eCRF is required and must be completed for each subject, with all required study data 
accurately recorded such that the information matches the data contained in medical records 
(eg, physicians’ notes, nurses’ notes, clinic charts, and other study-specific source 
documents). The eCRFs exist within a web-based EDC system managed by the data 
management contract research organization (CRO) for this study. After the investigator or 
the investigator’s designees (eg, research coordinators) have been appropriately trained, they 
will be given access to the EDC system and will enter the data required by the protocol into 
the EDC system. Any change of data will be made via the EDC system, with all changes 
tracked by the system to provide an audit trail. 
With an electronic signature, the investigator certifies that the data are complete and accurate 
prior to database lock. This electronic signature serves to attest that the information 
contained in the eCRFs is true. After database lock, the investigator site will receive a 
CD-ROM and/ or paper copies of the subject data for archiving at the investigator site. At all 
times, the principal investigator has final responsibility for the accuracy and authenticity of 
all clinical data entered onto the eCRFs and/or reported to PTC Therapeutics from the 
investigator site. 
10.5 
Study Records 
During the study, the investigator will maintain adequate records for the study, including 
medical records, source document records detailing the progress of the study for each 
subject, laboratory reports, a CD-ROM or paper copy of the data that have been captured in 
the EDC for each subject (eCRFs), paper CRFs, signed informed consent forms, study drug 
disposition records, correspondence with the IRB/EC, AE reports, and information regarding 
subject discontinuation and completion of the study. Current regulations require 
PTC Therapeutics (or an authorized designee) to inspect all documents and records required 
to be maintained by the investigator, including but not limited to medical records (office, 
clinic, or hospital) for the subjects enrolled in this study. These regulations also allow the 
same records to be inspected by regulatory authorities. 

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10.6 
Confidentiality 
Research records will be collected and stored in a manner that protects the confidentiality of 
subject information. The names and identities of all research subjects will be kept in strict 
confidence and will not appear on eCRFs, paper CRFs, or other records provided to or 
retained by PTC Therapeutics (or its authorized designee). The names and identities of the 
subjects need not be divulged; however, the records must nevertheless be inspected. This 
will be accomplished by redacting the subject’s name and replacing the name with the 
subject’s study ID number on any record provided to or retained by PTC Therapeutics. The 
informed consent form must include appropriate statements explaining these requirements. 
By signing this protocol, the investigator affirms to PTC Therapeutics that the investigator 
will maintain, in confidence, information furnished by PTC Therapeutics and will divulge 
such information to the IRB/EC under an appropriate understanding of confidentiality with 
such board. 
10.7 
Retention of Records 
To enable evaluations and/or audits from regulatory authorities or PTC Therapeutics, the 
investigator agrees to keep accurate and complete records, including the identity of all 
participating subjects (sufficient information to link eCRFs and clinic records), all original 
signed informed consent forms, CD-ROM or paper copies of the data that have been captured 
in the EDC for each subject (eCRFs), and detailed records of study drug disposition. All 
records and documents pertaining to the study (including but not limited to those outlined in 
Section 10.5) will be maintained by the investigator until notification is received from 
PTC Therapeutics that the records no longer need to be retained. 
The investigator must obtain written permission from PTC Therapeutics before disposing of 
any records. In order to avoid any possible errors, the investigator will contact PTC 
Therapeutics prior to the destruction of any study records. The investigator will promptly 
notify PTC Therapeutics in the event of accidental loss or destruction of any study records. 
If the investigator relocates, retires, or for any reason withdraws from the study, the study 
records may be transferred to an acceptable designee, such as another investigator, another 
institution, or to PTC Therapeutics. 
10.8 
Monitoring and Auditing 
In accordance with 21 Code of Federal Regulations Part 312.56 and/or relevant ICH 
guidelines, PTC Therapeutics or a designee will periodically inspect all eCRFs 
(see Section 10.4), study documents, research facilities, and clinical laboratory facilities 
associated with this study at mutually convenient times, before, during, and after completion 
of the study. As required by applicable regulations (Responsibilities of Sponsors and 
Investigators), the monitoring visits provide PTC Therapeutics with the opportunity to 
evaluate the progress of the study; verify the accuracy and completeness of data in the 
eCRFs; ensure that all protocol requirements, relevant regulations, and investigator’s 
obligations are being fulfilled; and resolve any inconsistencies in the study records. This 
includes inspection of all documents and records required to be maintained by the 
investigator, including but not limited to medical records (office, clinic, or hospital) for the 
subjects in this study. The names and identities of all research subjects will be kept in strict 
confidence and will not appear on eCRFs or other records provided to or retained by 

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PTC Therapeutics. The investigator/institution guarantees direct access to source documents 
by PTC Therapeutics and appropriate regulatory authorities. 
The investigator site may also be subject to review by the IRB/EC, to quality assurance 
audits performed by PTC Therapeutics or a designee, and/or to inspection by regulatory 
authorities. The GCP regulations also require the investigator to allow authorized 
representatives of regulatory authorities to inspect and make copies of the same records. 
It is important that the investigator and relevant institutional personnel are available during 
the monitoring visits and possible audits or inspections and that sufficient time is devoted to 
the process. 
10.9 
Termination of the Study 
PTC Therapeutics reserves the right to discontinue the study prior to inclusion of the 
intended number of subjects. The investigator, after consultation with the PTC Therapeutics 
medical monitor, reserves the right to discontinue the study at the investigator site for safety 
reasons at any time. 
After a decision to terminate the study, investigators must contact all subjects who are 
continuing their participation in the study and must do so within a timeperiod- set by 
PTC Therapeutics. As directed by PTC Therapeutics, all study materials must be collected 
and all electronic data entry forms completed to the greatest extent possible. 
10.10 
Public Notification of Study Conduct 
Consistent with requirements of the International Committee of Medical Journal Editors as a 
condition of consideration for publication of study results, PTC Therapeutics will be 
responsible for ensuring that this protocol is listed in the applicable clinical trials registry(s) 
and that information in the clinical trials registry(s) relating to study design and conduct is 
appropriately updated during the course of the study. In order to facilitate this process, 
investigators will need to supply PTC Therapeutics with appropriate contact information for 
investigator site personnel. 
10.11 
Dissemination of Results 
The information developed during the conduct of this clinical study is considered 
confidential by PTC Therapeutics. This information may be disclosed as deemed necessary 
by PTC Therapeutics. 
To allow for the use of the information derived from this clinical study and to ensure 
compliance with current regulations, the investigator is obliged to provide PTC Therapeutics 
with complete test results and all data developed in this study. The information obtained 
during this study may be made available by PTC Therapeutics to other physicians who are 
conducting similar studies and to regulatory authorities. Such information may be disclosed 
as deemed necessary by PTC Therapeutics. 

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PTC Therapeutics intends that the data from this study will be presented and published. The 
PTC Therapeutics staff under the direction of the PTC Therapeutics Chief Medical Officer or 
designee in collaboration with the investigator will be responsible for writing presentations 
and manuscripts for publication. Investigators will not be allowed to publish or present the 
data from this study without prior agreement with PTC Therapeutics. 
10.12 
Communication with Regulatory Authorities 
PTC Therapeutics (or designee) will assume responsibility for regulatory interactions with 
the applicable regulatory authorities. In fulfilling this responsibility, PTC Therapeutics (or a 
designee) will collect, assemble, and communicate all required regulatory documents 
(eg, investigator financial disclosure forms, protocol and protocol amendments, investigator 
brochures, informed consent documents, annual reports) as required by regulation. 
PTC Therapeutics (or a designee) will also assume responsibility for AE reporting to 
regulatory authorities as described in Section 7.11. 
11 
RATIONALE FOR STUDY DESIGN FEATURES 
11.1 
Endpoint Selection 
11.1.1 
Overview 
Endpoints have been selected based upon their ability to measure important aspects of DMD 
according to the scientific literature, their inclusion in regulatory guidance documents on 
clinical trials in DMD, their use in previous trials of ataluren and other investigational 
therapies for DMD, and/or their applicability across the age range of this study. Scientific 
advice from regulatory authorities and the efficacy results of Study 007 and Study 020 have 
also been considered in the selection of endpoints. 
11.1.2 
6-Minute Walk Test 
The 6MWT is an established outcome measure reflecting the global status of all the systems 
involved in walking, including the neuromuscular, pulmonary, and cardiovascular systems 
[Takeuchi 2008]. The 6MWT assesses walking ability and endurance, both of which are 
important in measuring the disease status of patients with DMD. Based on precedent for 
using the 6MWT as a primary outcome measure in registration-directed trials of other 
neuromuscular disorders [Rubin 2002, Wraith 2004, Muenzer 2006], PTC Therapeutics 
collaborated with the University of California-Davis to adapt the 6MWT to accommodate the 
physical and behavioral characteristics of children with DMD [McDonald 2010a]. 
Standardized guidelines for conduct of the 6MWT in the DMD population and multicenter 
training procedures for use in DMD clinical trials were developed [McDonald 2010a]. The 
6MWT was shown to be validated, feasible, accurate, and reproducible in the target 
population [McDonald 2010b]. Subsequently, the 6MWT has been extensively evaluated in 
DMD clinical trials and natural history studies [Mazzone 2011, Goemans 2013, 
Henricson 2013, Mazzone 2013, McDonald 2013a, McDonald 2013b, Pane 2014a, 
Pane 2014b, Pane 2014c, Mazzone 2016, Mercuri 2016, Willcocks 2016]. 

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11.1.3 
Timed Function Tests 
Timed function tests of running/walking 10 meters, climbing 4 stairs, and descending 4 stairs 
have been used for decades in DMD to monitor the progression of the disease and guide 
management of the patient [Brooke 1989, McDonald 1995]. Clinical evaluators in a 
multicentric setting are able to obtain highly reliable measurements [Mayhew 2007]. 
Worsening values have been correlated with time to wheelchair dependency and sensitivity 
to medical intervention has been shown [Mendell 1989, Griggs 1991, Beenakker 2005]. In 
addition, significant correlations between timed function test values and actual participation 
in daily life physical and social activities have been established [Bendixen 2014]. 
11.1.4 
North Star Ambulatory Assessment 
The NSAA is a functional scale specifically designed for ambulant DMD patients. The scale 
has been developed and piloted in the United Kingdom by the North Star Clinical Network 
for Paediatric Neuromuscular Disease Management with good intra- and inter-observer 
reliability and has recently been used in a large multicenter study [Mazzone 2011]. The scale 
consists of 17 items, ranging from standing (item 1) to running (item 17). It includes several 
items assessing abilities that are necessary to remain functionally ambulant; items assessing 
abilities, such as head raise and standing on heels, that can be partly present in the early 
stages of the disease; and a number of activities, such as hopping or running, that are 
generally never fully achieved in untreated boys with DMD but that have been found in those 
treated with daily steroids. 
11.1.5 
Myometry 
Myometric evaluation of limb strength is less sensitive than timed function tests to changes 
in disease status [Beenakker 2005]. Changes in muscle strength (as assessed by myometry) 
are most likely to be seen in DMD boys <7 years of age, while patients ≥7 years old show 
small changes in muscle strength by year, indicative of a floor effect. Because muscle 
strength is lost predominantly during earlier stages of the disease, a clearer effect of 
dystrophin replacement therapy on muscle strength may be expected in younger patients. For 
these reasons, myometry will be performed only in subjects <7 years of age. (Note: Upper 
limb function will be assessed in subjects ≥7 years old [Section 11.1.6]). 
In subjects <7 years of age, hand-held myometry will be employed to test knee extension and 
elbow flexion. These two muscle groups have shown the greatest test-retest reliability for 
quantitative myometry in boys with DMD [Mayhew 2007]. 
11.1.6 
Performance of Upper Limb (PUL) 
The PUL is a scale designed to measure motor performance of the upper limbs in DMD. The 
PUL was created within a conceptual framework reflecting the progression of weakness and 
natural history of functional decline evident in both the ambulant and non-ambulant stages of 
DMD. Modern psychometric methods were used to create a scale with robust internal 
reliability, validity, and hierarchical scalability; males with DMD and their families were 
involved iteratively throughout the process of the clinician-reported outcome assessment tool 
development to establish clinical meaningfulness and relevance of individual PUL items to 
activities of daily living [Mayhew 2013b]. The PUL includes 22 items (with an entry item to 
define starting functional level to avoid testing functional dimensions in which the patient 

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lacks the lower limit of function, and 21 items subdivided into shoulder level (4 items), 
elbow level (9 items), and distal level (8 items) dimensions. 
11.1.7 
DMD Upper Limb PROM 
The DMD Upper Limb PROM has been developed to assess disease progression in the upper 
limbs, beginning in the ambulatory stage of the disease through the transition to the non- 
ambulatory stage of the disease [Klingels 2016]. Thus, this outcome measure can provide 
information on the efficacy of ataluren even after subjects in the study lose ambulation. In 
addition, the DMD Upper Limb PROM provides information on activities of daily living that 
cannot otherwise be observed in a clinical or research setting (eg, feeding, washing, and 
leisure activities). This DMD-specific questionnaire includes 32 items categorized in 
4 domains of daily life: food (7 items), self-care (8 items), household and environment 
(6 items), and leisure and communication (11 items). The 32 items were selected, with input 
from DMD patients, physicians, physiotherapists, and sponsors, to cover a wide range of 
upper limb activities in daily life, from unimanual to bimanual activities and dexterity. The 
DMD Upper Limb PROM was designed for patients ≥7 years old, the age at which the 
maximum score is achieved by typically developing children. However, it is completed by a 
parent/caregiver until the patient is ≥16 years old. Excellent test-retest reliability (ICC=0.99) 
has been demonstrated [Klingels 2016]. 
11.1.8 
Magnetic Resonance Imaging 
Progressive fatty and fibrotic replacement of muscle due to an absence of dystrophin 
underlies the phenotypic manifestations of muscle weakness in boys with DMD. 
Quantitative MRI enables non-invasive, objective measurement of muscle pathophysiology 
in patients with DMD [Willcocks 2016]. 3-point Dixon imaging separates muscle fat and 
water based on phase difference (chemical shift) and provides measurement of muscle fat 
without any confounding effect of muscle edema. A standardized MRI protocol has been 
developed to facilitate image acquisition across multiple sites. Using centralized data 
analysis, quantitative evaluations of muscle fat fraction can be derived for leg muscles with 
important functional roles, such as the vastus lateralis. Inclusion of MRI in this trial offers 
the potential for tying an imaging biomarker to clinical benefit. Due to the need for specific 
equipment and trained operators, MRI will be conducted only at sites that have been 
qualified to perform this assessment based on access to the necessary equipment and trained 
operators. Although only a subset of sites will participate, it has been reported in the 
literature that the sensitivity of MRI may reduce the sample size needed to demonstrate a 
treatment effect, compared to functional outcome measures such as the 6MWT [Bonati 2015, 
Willcocks 2016]; this hypothesis remains to be confirmed. A limited number of MRI sites 
will also assess muscle fat fraction by MRS to explore the correlation between MRI and 
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11.1.9 
At-Home Questionnaires 
Regulatory guidelines for DMD clinical trials recommend assessment of subject- and 
parent/caregiver-reported HRQL [EMA 2015, FDA 2015]. Such information may help to 
confirm more objective measures of patient benefit, and document how drug activity 
translates to improved well-being outside of the clinic. The EQ-5D is a simple generic 
instrument developed by a multidisciplinary group of researchers, has been validated in many 
countries, and has been used to evaluate HRQL in patients with DMD [Cavazza 2016]. The 
DMD Self-Assessment Tool is a patient-reported outcome scale designed to measure 
functional ability in patients with DMD [Landfeldt 2015]. Both questionnaires will be 
completed at home, which may more accurately reflect the subject’s routine experience 
compared to in-clinic completion. These questionnaires will only be completed where 
validated versions in the local language are available. The questionnaires will be completed 
by the subject (where possible) and a parent/caregiver. 
11.1.10 
Safety Profiling 
As is conventional, safety will be characterized in terms of the type, incidence, timing, 
severity, drug-relatedness, and seriousness of AEs and laboratory abnormalities. For 
consistency of interpretation, AEs will be coded using the MedDRA, the severity of these 
events and laboratory abnormalities will be graded using the well-defined CTCAE and 
concomitant medications will be coded with the WHODRUG dictionary. 
11.1.11 
Study Drug Compliance 
Evaluation of study drug compliance provides context for assessments of efficacy and safety, 
and may offer a general indication of subject acceptance of therapy, integrating factors of 
tolerability, palatability, and convenience. The compliance of the subject will be verified by 
counting used drug study sachets. 
11.1.12 
Timing of Assessments 
The timing of study assessments is appropriate in the context of a chronic study. The 
12-week interval of subject visits permits inclusion of 6 post-baseline evaluations of efficacy 
during the randomized study period, ensuring that time trends can be adequately assessed and 
that sporadically missing data do not have a substantial impact on data analysis. Visits are 
paced sufficiently closely so that subjects and sites can become familiar with the routine of 
the study, but are sufficiently spaced so that learning and carryover effects are unlikely. 
Consideration has been given to the prospect that many subjects will need to travel 
considerable distances to study sites and that sites may achieve limiting capacity to 
accomplish study visits and data flow once multiple subjects are being followed 
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Study activities have been mapped across the study as outlined in the Schedule of Events 
(see Table 3 and Table 4) and within each study visit (see Study Manual); the intent is 
minimize variability by maintaining a clear and consistent approach to evaluations for each 
subject, across subjects at a site, and across sites. In particular, patient- and parent/caregiver- 
reported questionnaires are administered early, before later events in the day may influence 
reporting. 
11.2 
Subject Selection 
11.2.1 
General 
The eligibility criteria are designed to limit enrollment to subjects who clearly have DMD 
based on clinical, laboratory, and genetic findings but are sufficiently well (both in terms of 
DMD and in terms of concomitant illness) to safely participate in study procedures and 
provide interpretable results. Consistent with GCP guidelines, parents and subjects must 
provide informed consent/assent before initiation of any study procedures. To minimize 
missing data and premature discontinuations, subjects must have the personal and family 
resources to comply with study procedures and restrictions. In addition, subjects must not 
have serious concomitant conditions that would compromise safety, compliance, or 
evaluation. 
11.2.2 
DMD Diagnosis 
It is essential that subjects have a definite clinical and genetic diagnosis of DMD to justify 
the potential risks and inconvenience of involvement in the study. Mild patients are excluded 
by the requirement for disease presentation prior to age 6, in order to avoid difficulties in 
measuring a treatment effect within the 72-week treatment period. Restriction of enrollment 
to subjects with a nonsense mutation as the basis for DMD avoids the therapy of subjects 
who have no chance of benefit; it is known from prior studies with gentamicin that full- 
length protein production was seen only in subjects harboring a nonsense mutation as the 
exclusive basis for disease [Clancy 2001, Wilschanski 2003]. 
11.2.3 
Age 
This study will enroll patients ≥5 years old, consistent with the conditionally approved 
indication in Europe. However, the primary analysis will be conducted in a subset of patients 
who are ≥7 and ≤16 years old and meet additional criteria, as defined in Section 9.2.2. 
In DMD, disease-related progressive loss of muscle function occurs against the background 
of normal growth and development, where initial gains attributable to normal growth and 
development are eventually outpaced by losses due to disease progression [Henricson 2012]. 
A 1-year observational study of the 6MWT in patients with DMD and healthy controls 
(conducted by PTC Therapeutics in collaboration with Craig McDonald, MD, University of 
California-Davis) demonstrated that 6MWD in boys with DMD tends to improve up to age 7 
and decline due to disease progression thereafter [McDonald 2010a; McDonald 2010b]. This 
tendency for 6MWD to increase prior to age 7 and to decrease in older DMD patients was 
confirmed in a separate natural history study [Mazzone 2011]. In subjects who are 5 and 
6 years old, a treatment benefit may be obscured due to the confounding effect of normal 

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growth and development. Therefore, patients who are 5 and 6 years old are eligible for the 
study but will not be included in the primary analysis. 
Patients who are ≥16 years old and ambulatory at baseline may be considered to have a 
milder phenotype and a slower trajectory of disease progression. To limit the variability of 
study results, these patients will not be included in the primary analysis population. 
11.2.4 
Baseline 6MWD 
This study will enroll subjects with 6MWD ≥150 meters at pretreatment assessments. 
However, the primary analysis will be conducted in a subset of patients who have with 
6MWD ≥300 meters at pretreatment assessments and meet additional criteria, as defined in 
Section 9.2.2. 
The requirements that subjects enrolled in the study be able to walk 150 meters during the 
screening 6MWT provides an objective means to ensure that subjects are truly ambulatory, as 
ataluren is indicated for ambulatory patients with nmDMD. Assessing this distance is 
convenient because it constitutes 6 laps of a 25-meter course. 
Patients with baseline 6MWD <300 meters have a high muscle fat fraction and therefore a 
high risk of near-term loss of ambulation [Sweeney 2014]. To limit the variability of study 
results, these patients will not be included in the primary analysis population. 
11.2.5 
Baseline Timed Function Tests 
This study will enroll patients who are able to complete several timed function tests 
(run/walk 10 meters, climb 4 stairs, descend 4 stairs, and stand from supine) within 
30 seconds at pretreatment assessments. This inclusion criterion ensures that patients will be 
evaluable for changes from baseline in the timed function tests, which are important 
secondary endpoints in this study. 
Time to stand from supine significantly predicts for change in 6MWD, as demonstrated in 
two separate natural history studies [Goemans 2016, Mazzone 2016]. Patients who are able 
to stand from supine in <5 seconds are likely to remain relatively stable over the 72-week 
double-blind treatment period, potentially obscuring a treatment benefit in these patients. 
Therefore, these patients will not be included in the primary analysis population as defined in 
Section 9.2.2. 

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11.2.6 
Reproductive Considerations 
Ataluren is not genotoxic, did not affect fertility in male and female rats, and was not 
teratogenic in rats and rabbits. In addition, lack of sexual maturity in most of the subjects 
likely to be enrolled in this study limits reproductive risks. However, restriction on eligibility 
relating to willingness to avoid unprotected sexual intercourse in any subjects known to be 
sexually active is included as a general precaution. 
11.2.7 
Prior and Concomitant Therapies 
11.2.7.1 Corticosteroids 
Although not specifically approved by regulatory authorities for treatment of DMD, 
corticosteroids are commonly employed in this subject population [Matthews 2016]. 
Recently, a Centers for Disease Control and Prevention working group strongly urged 
consideration of corticosteroid therapy in all patients with DMD [Bushby 2010a]. A 
completed Phase 3 study of exon-skipping therapy in a subset of patients with DMD required 
corticosteroid use as an entry criterion [http://clinicaltrials.gov/ct2/show/NCT01254019]. 
Limiting eligibility to patients receiving a stable corticosteroid regimen of 
prednisone/prednisolone or deflazacort is expected to reduce the variability of slope of 
change in 6MWD (the primary endpoint), thereby minimizing the required sample size to 
demonstrate a statistically significant treatment effect and enhancing study feasibility. 
11.2.7.2 Other Prior and Concomitant Therapies 
Conventional supportive therapies will be permitted; however, efforts will be made to avoid 
use of concomitant medications that might confound interpretation of study results 
(eg, aminoglycosides) or pose a safety risk (immunosuppressive therapy other than 
corticosteroids). Ataluren has not proven to be allergenic in studies performed to date, but 
review of known allergies to excipients contained in the formulation is prudent. Other 
restrictions relating to recent use of experimental drugs or surgery allow candidates sufficient 
time to recover before proceeding to study drug dosing. Subjects are not permitted to enroll 
who have had changes in the use of ACE inhibitors or ARBs for the prophylaxis/treatment of 
cardiomyopathy within 1 month to start of study due to the potential to confound study 
results. Restrictions against enrollment of patients expected to have major surgical 
procedures during the course of the study or who have substantial respiratory or cardiac 
compromise are intended to avoid safety problems or gaps in study drug administration in 
patients who require intensive supportive care. 

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11.3 
Methods to Reduce Bias 
11.3.1 
Randomization 
Randomization is an accepted means to reduce bias and allows for the highest standard of 
evidence in documenting a treatment effect. The stratified, block randomization approach 
will be used. The system will assign the next available randomization number, within the list 
for the stratum, to the patient. Such a method allows treatment arms to be balanced with 
respect to the predefined stratification factors as well as for the number of subjects in each 
arm. The process will be established and performed centrally by an experienced CRO 
through an IRT system to maximize the integrity and security of the randomization and 
ensure appropriate access and convenience-of-use by the investigational sites. 
11.3.2 
Stratification 
The 3 stratification factors (type of concomitant corticosteroid use at baseline [deflazacort 
versus prednisone/prednisolone], baseline 6MWD [<300 meters versus ≥300 to <350 meters 
versus ≥350 to <400 meters versus ≥400 meters], and baseline time to stand from supine 
[<5 seconds versus ≥5 seconds]) are included to balance allocation of patients into treatment 
groups by these important parameters. 
Although not specifically approved by regulatory authorities for the treatment of DMD, the 
DMD Care Considerations Working Group strongly urges consideration of corticosteroid 
therapy in all patients who have DMD [Bushby 2010a]. Types of corticosteroids used in 
DMD included deflazacort, prednisolone, and prednisone. As prednisone is metabolized to 
prednisolone, prednisone and prednisolone are equipotent [Matthews 2016]. There is mixed 
evidence with respect to the comparative efficacy of deflazacort versus 
prednisone/prednisolone as treatments for DMD. Some reports have indicated that 
deflazacort and prednisone/prednisolone may be equivalent in improving motor function 
[Gloss 2016], while longer-term natural history data have associated use of deflazacort with 
later loss of ambulation [Bello 2015]. On the basis of the latter finding, stratification by 
deflazacort versus prednisone/prednisolone in DMD clinical trials has been recommended 
[Bello 2015]. 
DMD natural history studies have documented that baseline 6MWD is a significant predictor 
of change in 6MWD [Mazzone 2011, Goemans 2013, Mazzone 2013, McDonald 2013a, 
McDonald 2013b, Pane 2014a]. Therefore, it is important to ensure that the treatment arms 
are well balanced by baseline 6MWD. In the previous Phase 3 trial of ataluren for nmDMD, 
subgroup analyses showed a large treatment difference in patients with baseline 6MWD 
≥300 meters to <400 meters. Within the ≥300 meters to <400 meters stratum, further 
stratification by <350 vs ≥350 meters may be important to achieve the desired balance 
between treatment arms. In patients with less advanced disease severity (>400 meters at 
baseline), 6MWD is likely to remain stable over 1 year and therefore a treatment effect of 
disease stabilization/slowing can be obscured. In patients with more advanced disease 
severity (<300 meters at baseline), there is a high risk of loss of ambulation and loss of 
ability to perform functional outcome measures. 

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Baseline time to stand from supine also significantly predicts for change in 6MWD, 
independently of baseline 6MWD [Goemans 2016, Mazzone 2016], with poor performance 
on the time to stand from supine assessment increasing the risk of markedly negative changes 
in 6MWD and loss of ambulation. These results have identified time to stand from supine as 
an important additional prognostic factor of changes in 6MWD and more generally of disease 
progression [Mazzone 2016]. A threshold value of approximately 5 seconds appears to 
differentiate between patients who are likely to show stability or improvement versus those 
who are likely to decline [Goemans 2016]. These observations from natural history studies 
have been corroborated by analyses of data from our own previous placebo-controlled trials 
of ataluren. 
11.3.3 
Blinding 
Double-blind administration of study treatments is utilized to provide additional and 
substantial protection against motivational bias on the part of subjects, caregivers, clinic 
staff, and other study personnel, with respect to assessment of efficacy and safety parameters. 
Several steps have been taken in the proposed protocol design to minimize the prospect of 
systematic unblinding. Placebo is available that is an excellent match for both unmixed and 
mixed ataluren in terms of appearance, texture, taste, and odor. Brothers participating in the 
study will receive the same treatment group designation to minimize potential compromise of 
study drug blinding and to reduce the chance of dosing errors within families. 
Packaging and labeling is identical for both the active drug and placebo. Blinding will be 
done centrally rather than at sites. Access to randomization information during the course of 
the study will be restricted to the IRT system CRO. The focus of the interim safety reviews 
will be on blinded data without segregation by treatment group. The final unblinded analysis 
of the randomized phase of the study will only be performed when the data set is complete, 
and a snapshot has been frozen and archived. 
Unblinding in individual subjects who experience AEs is rarely required to provide effective 
intervention and support. Thus, disincentives for unblinding for AEs are included in the 
study. Investigational personnel will not have access to information at the site that would 
permit unblinding, and the individual subject randomization codes will only be obtainable 
through an auditable process involving the IRT system. Clinic staff will be made aware that 
such unblinding will preclude a subject from continuing with study drug administration. 
Unblinding will also require discussion between the investigator and the PTC Therapeutics 
medical monitor; this provision is not intended to prevent an investigator from proceeding 
with unblinding, but to ensure that appropriate consultation is obtained, that the investigator 
is aware of the consequences of the unblinding for the subject’s continued participation in the 
study, and that appropriate permission is granted to the IRT system to release the treatment 
assignment only for that subject. 

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11.4 
Treatment and Safety Monitoring Plan 
11.4.1 
Reference Therapy 
Selection of placebo as the reference arm in the proposed study is clearly appropriate given 
that no other approved standard therapy for nmDMD exists. Use of placebo provides an 
opportunity to obtain additional information regarding the full treatment effect size for 
ataluren. 
11.4.2 
Schedule and Dose Selection 
Dosing based on body weight will continue to be employed. Such dosing is common in 
pediatrics and reduces variability in exposure by accommodating differences in subject size 
across the span of ages of the boys who will participate in the clinical study program. 
The schedule of drug administration is derived directly from Phase 1 pharmacokinetics 
modeling and from Phase 2 exposure information. The intent of administering 2 smaller 
doses at 6-hour intervals during the day and a larger dose at a 12hour interval overnight 
(eg-, at 7:00 AM, 1:00 PM, and 7:00 PM) is to optimally sustain target plasma concentrations 
while minimizing total exposures. This schedule is likely to fit well with daily patterns of 
living for subjects, thus enhancing compliance. As confirmation of that premise, compliance 
with ataluren dosing in previous trials has been excellent. 
The dose of 40 mg/kg/day is the conditionally approved dose of ataluren for DMD in Europe. 
11.4.3 
Duration of Therapy 
Duration of therapy in this confirmatory study is consistent with the EMA and FDA 
guidelines for DMD clinical trial, which indicate that a duration of therapy >1 year may be 
necessary to demonstrate a treatment effect. Use of a placebo control beyond 72 weeks 
would likely be discouraging to subjects and could compromise subject participation and 
retention. After the double-blind treatment period ends, subjects will receive an additional 
72 weeks of open-label treatment to evaluate long-term effects of ataluren on patients with 
this progressive disorder. 
11.4.4 
Safety Monitoring 
In defining therapeutic activity in a particular clinical setting, it is imperative that the drug’s 
safety profile be fully characterized. As is conventional in all clinical studies, proper 
description of each AE or laboratory abnormality requires an understanding of the type, 
incidence, timing, severity, and relatedness to study drug. For consistency of interpretation, 
AEs will be coded using the standard MedDRA, and the severity of these events will be 
graded using the well - defined CTCAE. Standard definitions for seriousness will be applied. 
Particular attention will be paid to any AEs causing discontinuation of ataluren and to SAEs 
requiring rapid regulatory reporting. 

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11.4.5 
Concomitant Therapies 
As substantial modification of corticosteroid dosing due to manifestation of undesirable side 
effects such as osteoporosis during the study may confound study results, investigators and 
subjects are encouraged to maintain corticosteroid dosing as uniformly as possible. Specific 
recommendations for maintaining, modifying, or discontinuing corticosteroids are provided 
with the protocol (see Appendix 1). 
Cases of decreased renal function have been observed in patients with nmCF receiving 
ataluren and IV aminoglycosides together with other antibiotics for cystic fibrosis 
exacerbations (Section 5.4.2). As a precaution, guidance has been provided to the 
investigator with respect to actions to be taken in the event that abnormalities are noted in 
renal laboratory parameters. 
The investigator is encouraged to consult the PTC medical monitor with questions relating to 
specific drugs and their potential for interactions with ataluren. 
11.5 
Open-Label Treatment Period 
The inclusion of a 72-week open-label treatment period following 72 weeks of double-blind 
treatment will allow for collection of long-term efficacy data and add to the long-term safety 
database. 
The open-label treatment period is important for subject recruitment, retention, and 
compliance in this double-blind study. The assurance that all subjects can eventually receive 
open-label ataluren if they participate in the double-blind study will stimulate subject 
recruitment. The knowledge that subjects must be reasonably compliant with study 
procedures and persist with therapy throughout the double-blind study unless medical 
contraindications supervene provides strong incentives for subject reliability and retention. 
The understanding by parents that actions to break the blind (eg, having study medication 
chemically analyzed) will result in forfeiture of participation in the open-label treatment 
period will help to preserve the integrity of the blinding. 

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12 
PROTOCOL VERSION HISTORY 
Version 1: 23 February 2017 
Version 2: 04 October 2017 
Version 3: 01 August 2019 
Version 4: 21 July 2020 
12.1 
Version 4.0: 21 July 2020 
 
Item 
No. 
Protocol Section Version 4/Update 
Reason/Rationale 
1 
Protocol 
Identifiers and 
Study Personnel 
Revised list of study personnel and protocol number 
and date 
Clarification 
2 
3.2 
Revised phrasing of assessment timepoints 
Clarification 
3 
4.1 
Revised text to indicate enrollment targets are 
approximate 
Clarification 
4 
6.1 
Updated Schedule of Events to reflect that subjects 
transitioning to another ataluren study do not require 
a post-treatment follow-up visit 
Clarification 
5 
6.2.1.5 
Added language indicating that subjects who 
continue to receive post-study access to ataluren are 
not required to have a follow-up visit. 
Clarification 
6 
6.2.10 
Clarified that the Central Laboratory Manual 
provides detail on the timing of collection of 
pharmacokinetic samples 
Clarification 
7 
7.6 
Added that PTC Pharmacovigilance is also to be 
notified of pregnancy outcomes and that this 
notification is to occur within 24 hours. 
Update 
8 
9.1 
Added the word “approximately” for consistency with 
Section 4.1 
Clarification 
9 
12 
Updated protocol version history to reflect version 4 
Update 

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12.2 
Version 3.0: 01 August 2019 
The overall reason for Version 3: The overall reasons for Version 3 were to address 
regulatory feedback and to provide updates. 
 
Item 
No. 
Protocol Section 
Version 3/Update 
Reason/Rationale 
1 
Protocol 
Document date/version were updated 
Update 
2 
Protocol Identifiers 
and Study Personnel 
Study personnel updated 
Update 
3 
2.1.2 
Added secondary objectives: 
• Evaluate the correlation between plasma 
concentration of ataluren and functional 
outcomes 
• to evaluate plasma pharmacokinetic (PK) 
profile of ataluren 
Update 
4 
2.2.2.1 
Added: 
• Plasma PK at pre-morning dose and 2 
hours post-morning dose at Week 144 
Update 
5 
3.2, #3, #7 
3. Added: “When Version 3 is implemented or 
approximately 270 subjects have enrolled in 
the study, only subjects aged ≥7 to ≤16 who 
meet the mITT criteria will be eligible to enroll.” 
7. Added: “When Version 3 is implemented or 
approximately 270 subjects have enrolled in 
the study, only subjects who meet the mITT, 
6MWD ≥300 meters at screening, Baseline 
Day 1, and Baseline Day 2 and time to stand 
from supine ≥5 seconds at Baseline Day 1 and 
Baseline Day 2, will be eligible to enroll.” 
Update 
6 
4.1 
Number enrolled/sample size increased from 
~250 to a maximum of 340 subjects; the 
maximum sample size of 340 subjects will 
include up to 162 subjects who meet the mITT 
criteria; deleted phrase that subjects who do 
not meet the mITT will be included in the ITT. 
Update 
7 
6.1, Table 4 
Added PK samples on Day 144 
Update 
8 
6.2.7 
Added thrombospondin 1 (THBS1) as a marker 
Update 
9 
6.2.10 
Added PK analysis method and sampling details Update 
10 
6.3 
Increased the amount of blood drawn 
Update 
11 
7.9, Table 7 
Table of AE reporting revised 
Update 
12 
7.10 
SAE reporting contact information updated 
Update 
13 
9.1 
Increased sample size 
Update 
14 
9.4.8 
Added PK statistical analysis methods 
Update 
15 
9.5 
Revised timing of analyses 
Update 
16 
12 
Added Protocol Version History 
Update 

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13 
BIBLIOGRAPHY 
Aartsma-Rus A, Van Deutekom JC, Fokkema IF, Van Ommen GJ, Den Dunnen JT. Entries 
in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation 
types and paradoxical cases that confirm the reading-frame rule. Muscle Nerve. 2006 
Aug;34(2):135-44. 
Beenakker EA, Maurits NM, Fock JM, Brouwer OF, van der Hoeven JH. Functional ability 
and muscle force in healthy children and ambulant Duchenne muscular dystrophy patients. 
Eur J Paediatr Neurol. 2005b;9(6):387-93. 
Bello L, Gordish-Dressman H, Morgenroth LP, Henricson EK, Duong T, Hoffman EP, 
Cnaan A, McDonald CM; CINRG Investigators. Prednisone/prednisolone and deflazacort 
regimens in the CINRG Duchenne Natural History Study. Neurology. 2015 Sep 
22;85(12):1048-55. 
Bendixen RM, Lott DJ, Senesac C, Mathur S, Vandenborne K. Participation in daily life 
activities and its relationship to strength and functional measures in boys with Duchenne 
muscular dystrophy. Disabil Rehabil. 2014;36(22):1918-23. 
Bladen CL, Salgado D, Monges S, Foncuberta ME, Kekou K, Kosma K, et al. The TREAT- 
NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy 
mutations. Hum Mutat. 2015 Apr;36(4):395-402. 
Bonati U, Hafner P, Schädelin S, Schmid M, Naduvilekoot Devasia A, Schroeder J, Zuesli S, 
Pohlman U, Neuhaus C, Klein A, Sinnreich M, Haas T, Gloor M, Bieri O, Fischmann A, 
Fischer D. Quantitative muscle MRI: A powerful surrogate outcome measure in Duchenne 
muscular dystrophy. Neuromuscul Disord. 2015 Sep;25(9):679-85. 
Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Florence J, King WM, 
Pandya S, Robison J, Schierbecker J, et al. Duchenne muscular dystrophy: patterns of clinical 
progression and effects of supportive therapy. Neurology. 1989 Apr;39(4):475-81. 
Bushby K. Duchenne muscular dystrophy: double-blind, randomized trial to find optimum 
steroid regimen. 2007. 
Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, 
McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C; DMD Care 
Considerations Working Group. Diagnosis and management of Duchenne muscular 
dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet 
Neurol. 2010a Jan;9(1):77-93. 
Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, 
McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C; DMD Care 
Considerations Working Group. Diagnosis and management of Duchenne muscular 
dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol. 2010b 
Feb;9(2):177-89. 
Cavazza M, Kodra Y, Armeni P, De Santis M, López-Bastida J, Linertová R, Oliva-Moreno 
J, Serrano-Aguilar P, Posada-de-la-Paz M, Taruscio D, Schieppati A, Iskrov G, Péntek M, 
von der Schulenburg JM, Kanavos P, Chevreul K, Persson U, Fattore G; BURQOL-RD 
Research Network. Social/economic costs and health-related quality of life in patients with 
Duchenne muscular dystrophy in Europe. Eur J Health Econ. 2016 Apr;17 Suppl 1:19-29 

PTC124-GD-041-DMD 
Clinical Protocol 
V4.0 
PTC Therapeutics - Confidential 
Page 71 of 80 
 
 
Clancy JP, Bebok Z, Ruiz F, King C, Jones J, Walker L, Greer H, Hong J, Wing L, Macaluso 
M, Lyrene R, Sorscher EJ, Bedwell DM. Evidence that systemic gentamicin suppresses 
premature stop mutations in patients with cystic fibrosis. Am J Respir Crit Care Med. 2001 
Jun;163(7):1683-92. 
El-Aloul B, Altamirano-Diaz L, Zapata-Aldana E, Rodrigues R, Malvankar-Mehta MS, 
Nguyen CT, Campbell C. Pharmacological therapy for the prevention and management of 
cardiomyopathy in Duchenne muscular dystrophy: A systematic review. Neuromuscul 
Disord. 2016 Oct 11. 
European Medicines Agency. EMA guideline on the investigation of drug interactions. 2012. 
European Medicines Agency. EMA guideline on the clinical investigation of medicinal 
products for the treatment of Duchenne and Becker muscular dystrophy. 2015. 
Finder JD, Birnkrant D, Carl J, Farber HJ, Gozal D, Iannaccone ST, Kovesi T, Kravitz RM, 
Panitch H, Schramm C, Schroth M, Sharma G, Sievers L, Silvestri JM, Sterni L; American 
Thoracic Society. Respiratory care of the patient with Duchenne muscular dystrophy: ATS 
consensus statement. Am J Respir Crit Care Med. 2004 Aug 15;170(4):456-65. 
Food and Drug Administration. FDA draft guidance on Duchenne muscular dystrophy and 
related dystrophinopathies: developing drugs for treatment. 2015. 
Gloss D, Moxley RT 3rd, Ashwal S, Oskoui M. Practice guideline update summary: 
Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline 
Development Subcommittee of the American Academy of Neurology. Neurology. 2016 Feb 
2;86(5):465-72. 
Goemans N, van den Hauwe M, Wilson R, van Impe A, Klingels K, Buyse G. Ambulatory 
capacity and disease progression as measured by the 6-minute-walk-distance in Duchenne 
muscular dystrophy subjects on daily corticosteroids. Neuromuscul Disord. 2013 
Aug;23(8):618-23. 
Goemans N, Vanden Hauwe M, Signorovitch J, Swallow E, Song J; Collaborative Trajectory 
Analysis Project (cTAP). Individualized prediction of changes in 6-minute walk distance for 
patients with Duchenne muscular dystrophy. PLoS One. 2016 Oct 13;11(10):e0164684. 
Griggs RC, Moxley RT 3rd, Mendell JR, Fenichel GM, Brooke MH, Pestronk A, Miller JP. 
Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course 
and dose response. Clinical Investigation of Duchenne Dystrophy Group. Arch Neurol. 1991 
Apr; 48(4): 383-8. 
Henricson E, Abresch R, Han JJ, Nicorici A, Goude Keller E, Elfring G, Reha A, Barth J, 
McDonald CM. Percent-predicted 6-minute walk distance in Duchenne muscular dystrophy 
to account for maturational influences. Version 2. PLoS Curr. 2012 Jan 25 [revised 2012 Feb 
2];4:RRN1297. 
Henricson E, Abresch R, Han JJ, Nicorici A, Goude Keller E, de Bie E, McDonald CM. The 
6-minute walk test and person-reported outcomes in boys with Duchenne muscular dystrophy 
and typically developing controls: longitudinal comparisons and clinically-meaningful 
changes over one year. PLoS Curr. 2013 Jul 8;5. 

PTC124-GD-041-DMD 
Clinical Protocol 
V4.0 
PTC Therapeutics - Confidential 
Page 72 of 80 
 
 
Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and 
management of chronic heart failure in the adult: executive summary. A report of the 
American College of Cardiology/American Heart Association Task Force on Practice 
Guidelines (Committee to revise the 1995 Guidelines for the Evaluation and Management of 
Heart Failure). J Am Coll Cardiol 2001 Dec;38:2101-13. 
International Conference on Harmonisation. ICH Harmonised Tripartite Guideline: Guideline 
for Good Clinical Practice E6 (R1), Step 4. 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/St 
ep4/E6_R1 Guideline.pdf. 6-10-1996 
Klingels K, Mayhew AG, Mazzone ES, Duong T, Decostre V, Werlauff U, Vroom E, 
Mercuri E, Goemans NM; Upper Limb Clinical Outcome Group. Development of a patient- 
reported outcome measure for upper limb function in Duchenne muscular dystrophy: DMD 
Upper Limb PROM. Dev Med Child Neurol. 2016 Sep 26. 
Landfeldt E, Mayhew A, Eagle M, Lindgren P, Bell CF, Guglieri M, Straub V, Lochmüller 
H, Bushby K. Development and psychometric analysis of the Duchenne muscular dystrophy 
Functional Ability Self-Assessment Tool (DMDSAT). Neuromuscul Disord. 2015 
Dec;25(12):937-44. 
Matthews E, Brassington R, Kuntzer T, Jichi F, Manzur AY. Corticosteroids for the 
treatment of Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2016 May 
5;(5):CD003725. 
Mayhew JE, Florence JM, Mayhew TP, Henricson EK, Leshner RT, McCarter RJ, Escolar 
DM. Reliable surrogate outcome measures in multicenter clinical trials of Duchenne 
muscular dystrophy. Muscle Nerve. 2007 Jan;35(1):36-42. 
Mayhew AG, Cano SJ, Scott E, Eagle M, Bushby K, Manzur A, Muntoni F; North Star 
Clinical Network for Neuromuscular Disease. Detecting meaningful change using the North 
Star Ambulatory Assessment in Duchenne muscular dystrophy. Dev Med Child Neurol. 
2013a Nov;55(11):1046-52. 
Mayhew A, Mazzone ES, Eagle M, Duong T, Ash M, Decostre V, Vandenhauwe M, 
Klingels K, Florence J, Main M, Bianco F, Henrikson E, Servais L, Campion G, Vroom E, 
Ricotti V, Goemans N, McDonald C, Mercuri E; Performance of the Upper Limb Working 
Group. Development of the Performance of the Upper Limb module for Duchenne muscular 
dystrophy. Dev Med Child Neurol. 2013b Nov;55(11):1038-45. 
Mazzone E, Vasco G, Sormani MP, Torrente Y, Berardinelli A, Messina S, D'Amico A, 
Doglio L, Politano L, Cavallaro F, Frosini S, Bello L, Bonfiglio S, Zucchini E, De Sanctis R, 
Scutifero M, Bianco F, Rossi F, Motta MC, Sacco A, Donati MA, Mongini T, Pini A, Battini 
R, Pegoraro E, Pane M, Gasperini S, Previtali S, Napolitano S, Martinelli D, Bruno C, Vita 
G, Comi G, Bertini E, Mercuri E. Functional changes in Duchenne muscular dystrophy: a 12- 
month longitudinal cohort study. Neurology. 2011 Jul 19;77(3):250-6. 
Mazzone ES, Pane M, Sormani MP, Scalise R, Berardinelli A, Messina S, Torrente Y, 
D'Amico A, Doglio L, Viggiano E, D'Ambrosio P, Cavallaro F, Frosini S, Bello L, Bonfiglio 
S, De Sanctis R, Rolle E, Bianco F, Magri F, Rossi F, Vasco G, Vita G, Motta MC, Donati 
MA, Sacchini M, Mongini T, Pini A, Battini R, Pegoraro E, Previtali S, Napolitano S, Bruno 

PTC124-GD-041-DMD 
Clinical Protocol 
V4.0 
PTC Therapeutics - Confidential 
Page 73 of 80 
 
 
C, Politano L, Comi GP, Bertini E, Mercuri E. 24 month longitudinal data in ambulant boys 
with Duchenne muscular dystrophy. PLoS One. 2013;8(1):e52512. 
Mazzone ES, Coratti G, Sormani MP, Messina S, Pane M, D'Amico A, Colia G, Fanelli L, 
Berardinelli A, Gardani A, Lanzillotta V, D'Ambrosio P, Petillo R, Cavallaro F, Frosini S, 
Bello L, Bonfiglio S, De Sanctis R, Rolle E, Forcina N, Magri F, Vita G, Palermo C, Donati 
MA, Procopio E, Arnoldi MT, Baranello G, Mongini T, Pini A, Battini R, Pegoraro E, 
Torrente Y, Previtali SC, Bruno C, Politano L, Comi GP, D'Angelo MG, Bertini E, Mercuri 
E. Timed Rise from Floor as a Predictor of Disease Progression in Duchenne Muscular 
Dystrophy: An Observational Study. PLoS One. 2016 Mar 16;11(3):e0151445. 
McDonald CM, Abresch RT, Carter GT, Fowler WM Jr, Johnson ER, Kilmer DD, Sigford 
BJ. Profiles of neuromuscular diseases. Duchenne muscular dystrophy. Am J Phys Med 
Rehabil. 1995 Sep-Oct;74(5 Suppl):S70-92. 
McDonald CM, Henricson EK, Han JJ, Abresch RT, Nicorici A, Elfring GL, Atkinson L, 
Reha A, Hirawat S, Miller LL. The 6-minute walk test as a new outcome measure in 
Duchenne muscular dystrophy. Muscle Nerve. 2010a Apr;41(4): 500-10. 
McDonald CM, Henricson EK, Han JJ, Abresch RT, Nicorici A, Elfring GL, Atkinson L, 
Reha A, Hirawat S, Miler LL. The 6-minute walk test in Duchenne/Becker muscular 
dystrophy: longitudinal observations. Muscle Nerve. 2010b Dec;42(6): 966-74. 
McDonald CM, Henricson EK, RT Abresch, et al. The 6-minute walk test and other 
endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 
weeks from a multicenter study. Muscle Nerve. 2013a Sep;48(3):343-356. 
McDonald CM, Henricson EK, RT Abresch, et al. The 6-minute walk test and other clinical 
endpoints in Duchenne muscular dystrophy: reliability, concurrent validity, and minimal 
clinically important differences from a multicenter study. Muscle Nerve. 2013b 
Sep;48(3):357-368. 
Mendell JR, Moxley RT, Griggs RC, Brooke MH, Fenichel GM, Miller JP, King W, Signore 
L, Pandya S, Florence J, et al. Randomized, double-blind six-month trial of prednisone in 
Duchenne's muscular dystrophy. N Engl J Med. 1989 Jun 15;320(24):1592-7. 
Mercuri E, Signorovitch JE, Swallow E, Song J, Ward SJ; DMD Italian Group.; Trajectory 
Analysis Project (cTAP). Categorizing natural history trajectories of ambulatory function 
measured by the 6-minute walk distance in patients with Duchenne muscular dystrophy. 
Neuromuscul Disord. 2016 Sep;26(9):576-83. 
Merlini L, Sabatelli P. Improving clinical trial design for Duchenne muscular dystrophy. 
BMC Neurol. 2015 Aug 26;15:153. 
Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM, Vellodi A, Martin R, 
Ramaswami U, Gucsavas-Calikoglu M, Vijayaraghavan S, Wendt S, Puga AC, Ulbrich B, 
Shinawi M, Cleary M, Piper D, Conway AM, Kimura A. A phase II/III clinical study of 
enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter 
syndrome). Genet Med. 2006 Aug;8(8):465-73. Erratum in: Genet Med. 2006 Sep;8(9):599. 

PTC124-GD-041-DMD 
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V4.0 
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Page 74 of 80 
 
 
Pane M, Mazzone ES, Sivo S, Sormani MP, Messina S, D Amico A, Carlesi A, Vita G, 
Fanelli L, Berardinelli A, Torrente Y, Lanzillotta V, Viggiano E, D Ambrosio P, Cavallaro F, 
Frosini S, Barp A, Bonfiglio S, Scalise R, De Sanctis R, Rolle E, Graziano A, Magri F, 
Palermo C, Rossi F, Donati MA, Sacchini M, Arnoldi MT, Baranello G, Mongini T, Pini A, 
Battini R, Pegoraro E, Previtali S, Bruno C, Politano L, Comi GP, Bertini E, Mercuri E. Long 
term natural history data in ambulant boys with Duchenne muscular dystrophy: 36-month 
changes. PLoS One. 2014a Oct 1;9(10):e108205. 
Pane M, Mazzone ES, Sivo S, Fanelli L, De Sanctis R, D'Amico A, Messina S, Battini R, 
Bianco F, Scutifero M, Petillo R, Frosini S, Scalise R, Vita GL, Bruno C, Pedemonte M, 
Mongini T, Pegoraro E, Brustia F, Gardani A, Berardinelli A, Lanzillotta V, Viggiano E, 
Cavallaro F, Sframeli M, Bello L, Barp A, Busato F, Bonfiglio S, Rolle E, Colia G, Bonetti 
A, Palermo C, Graziano A, D'Angelo G, Pini A, Corlatti A, Gorni K, Baranello G, Antonaci 
L, Bertini E, Politano L, Mercuri E. PLoS Curr. The 6 minute walk test and performance of 
upper limb in ambulant Duchenne muscular dystrophy boys. 2014b Oct 7;6. pii: 
ecurrents.md.a93d9904d57dcb08936f2ea89bca6fe6. 
Pane M, Mazzone ES, Sormani MP, Messina S, Vita GL, Fanelli L, Berardinelli A, Torrente 
Y, D'Amico A, Lanzillotta V, Viggiano E, D'Ambrosio P, Cavallaro F, Frosini S, Bello L, 
Bonfiglio S, Scalise R, De Sanctis R, Rolle E, Bianco F, Van der Haawue M, Magri F, 
Palermo C, Rossi F, Donati MA, Alfonsi C, Sacchini M, Arnoldi MT, Baranello G, Mongini 
T, Pini A, Battini R, Pegoraro E, Previtali SC, Napolitano S, Bruno C, Politano L, Comi GP, 
Bertini E, Morandi L, Gualandi F, Ferlini A, Goemans N, Mercuri E. 6-minute walk test in 
Duchenne MD patients with different mutations: 12 month changes. PLoS One. 2014c Jan 
8;9(1):e83400. 
Passamano L, Taglia A, Palladino A, Viggiano E, D'Ambrosio P, Scutifero M, Rosaria Cecio 
M, Torre V, DE Luca F, Picillo E, Paciello O, Piluso G, Nigro G, Politano L. Improvement 
of survival in Duchenne Muscular Dystrophy: retrospective analysis of 835 patients. Acta 
Myol. 2012 Oct;31(2):121-5. 
Petrof BJ, Shrager JB, Stedman HH, Kelly AM, Sweeney HL. Dystrophin protects the 
sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci U S A. 
1993 Apr 15;90(8):3710-4. 
Raman SV, Hor KN, Mazur W, Halnon NJ, Kissel JT, He X, Tran T, Smart S, McCarthy B, 
Taylor MD, Jefferies JL, Rafael-Fortney JA, Lowe J, Roble SL, Cripe LH. Eplerenone for 
early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, 
placebo-controlled trial. Lancet Neurol. 2015 Feb;14(2):153-61. 
Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A, Pulido T, Frost A, Roux S, 
Leconte I, Landzberg M, Simonneau G. Bosentan therapy for pulmonary arterial 
hypertension. N Engl J Med. 2002 Mar 21;346(12):896-903. Erratum in: N Engl J Med 2002 
Apr 18;346(16):1258. 
Sweeney HL. Developing skeletal muscle MRI/MRS as a biomarker for DMD therapeutic 
development. 2014 Annual Connect Conference, Chicago, IL. 
Takeuchi Y, Katsuno M, Banno H, Suzuki K, Kawashima M, Atsuta N, Ito M, Watanabe H, 
Tanaka F, Sobue G. Walking capacity evaluated by the 6-minute walk test in spinal and 
bulbar muscular atrophy. Muscle Nerve. 2008 Aug;38(2):964-71. 

PTC124-GD-041-DMD 
Clinical Protocol 
V4.0 
PTC Therapeutics - Confidential 
Page 75 of 80 
 
 
Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ, Trifillis P, Paushkin S, Patel M, 
Trotta CR, Hwang S, Wilde RG, Karp G, Takasugi J, Chen G, Jones S, Ren H, Moon YC, 
Corson D, Turpoff AA, Campbell JA, Conn MM, Khan A, Almstead NG, Hedrick J, Mollin 
A, Risher N, Weetall M, Yeh S, Branstrom AA, Colacino JM, Babiak J, Ju WD, Hirawat S, 
Northcutt VJ, Miller LL, Spatrick P, He F, Kawana M, Feng H, Jacobson A, Peltz SW, 
Sweeney HL. PTC124 targets genetic disorders caused by nonsense mutations. Nature. 2007 
May 3;447(7140):87-91. 
Willcocks RJ, Rooney WD, Triplett WT, Forbes SC, Lott DJ, Senesac CR, Daniels MJ, 
Wang DJ, Harrington AT, Tennekoon GI, Russman BS, Finanger EL, Byrne BJ, Finkel RS, 
Walter GA, Sweeney HL, Vandenborne K. Multicenter prospective longitudinal study of 
magnetic resonance biomarkers in a large Duchenne muscular dystrophy cohort. Ann Neurol. 
2016 Apr;79(4):535-47. 
Wilschanski M, Yahav Y, Yaacov Y, Blau H, Bentur L, Rivlin J, Aviram M, Bdolah-Abram 
T, Bebok Z, Shushi L, Kerem B, Kerem E. Gentamicin-induced correction of CFTR function 
in patients with cystic fibrosis and CFTR stop mutations. N Engl J Med. 2003 Oct 
9;349(15):1433-41. 
Wraith JE, Clarke LA, beck M, Kolodny EH, Pastores GM, Muenzer J, rapoport DM, Berger 
KI, Swiedler SJ, Kakkis ED, Braakman T, Chadbourne E, Walton-Bowen K, Cox GF. 
Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, 
placebo-controlled, multinational study of recombinant human alpha-L-iduronidase 
(laronidase). J Pediatr. 2004 May;144(5): 581-8. 

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APPENDIX 1 MANAGEMENT OF CORTICOSTEROIDS 
A. 
Initiating Alternate Corticosteroids During the Study 
If a subject does require initiation of an alternate corticosteroid therapy (ie. switching from 
prednisone to deflazacort or vice-versa) during the study, total doses should not exceed 
0.75 mg/kg for prednisone and 0.9 mg/kg for deflazacort. General recommendations for 
corticosteroid dosing are provided in Table A below. 
Table A. 
Guidance for Initiating Alternate Corticosteroid Treatment 
 
Weight Range 
Prednisone Dose 
(0.75 mg/kg) 
Deflazacort Dose 
(0.9 mg/kg) 
15-19 kg 
12 mg 
15 mg 
20-25 kg 
17 mg 
21 mg 
26-32 kg 
22 mg 
27 mg 
33-39 kg 
27 mg 
33 mg 
40 kg+ 
30 mg 
36 mg 
Subjects who require alternate corticosteroid initiation may remain on blinded study drug 
therapy. Changing the type of corticosteroid or the corticosteroid schedule during the study is 
strongly discouraged. 
B. 
Maintaining Corticosteroid Dosage During the Study 
Adjustments in corticosteroid dosage for increases in body weight are permitted but are not 
mandatory. If it is the practice of the investigator to adjust subjects’ corticosteroid doses for 
changes in body weight, total doses should not exceed 0.75 mg/kg for prednisone and 
0.9 mg/kg for deflazacort (see Table A above). 
In addition, consistent with the standards proposed for the planned international 
corticosteroid optimization study [Bushby 2007], increases in total dose for any reasons 
should not exceed 5 mg for prednisone or 6 mg for deflazacort. For example, if a subject is 
receiving 22 mg QD of prednisone and it is elected to increase the dose, the total prednisone 
dose should not be increased beyond 27 mg QD. In addition, for subjects ≥40 kg, total doses 
should be capped at 30 mg of prednisone or 36 mg of deflazacort unless the subject was 
already receiving a higher dose of corticosteroids than these limits at study entry 
[Bushby 2007]. 
Subjects who require corticosteroid increases may remain on blinded study drug therapy. 
C. 
Modifying Corticosteroid Dosage During the Study 
Discontinuation of corticosteroid therapy during the study should be avoided unless clinically 
necessary. In the case of the development of predictable corticosteroid-related side effects, 
appropriate supportive care should be provided and corticosteroid dosage can be maintained 
(ie, not increased for the normal increase in body weight). If unacceptable corticosteroid side 
effects persist, the dosage can be reduced in decrements of ≤5 mg total dose for prednisone 
(≤6 mg total dose for deflazacort). Finally, corticosteroid administration can be stopped 
altogether. Specific recommendations for precautionary interventions for specific 
corticosteroid-related AEs are given below. 

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Acne 
In the event of bothersome acne that may be attributable to corticosteroids, the following 
interventions are recommended: 
● 
Corticosteroids should not to be increased to adjust for increases in body weight 
and the subject should be provided with consultation from a dermatologist for 
institution of appropriate conventional therapy for acne. 
● 
If the acne is so severe it cannot be managed with appropriate anti-acne measures, 
dosage reductions of ≤5 mg total dose for prednisone (≤6 mg total dose for 
deflazacort) at ~6-week intervals can be considered. 
● 
Every attempt should be made to avoid stopping corticosteroids solely for acne; if 
the subject/family demands that corticosteroids be stopped, see Section D below 
for procedures for withdrawal of corticosteroids. 
Behavior Changes 
Where behavior changes are disruptive to family/school life, the following interventions are 
recommended: 
● 
The subject and the family should be provided with behavioral support from a 
child psychologist. 
● 
If the subject is already receiving behavioral advice under the guidance of a child 
psychologist, the corticosteroid dosage should not to be increased to adjust for 
increases in body weight. Consideration can be given to administering the 
corticosteroid dose at night instead of in the morning. 
● 
If there is no improvement despite behavioral advice under the guidance of a child 
psychologist, dosage reductions of ≤5 mg total dose for prednisone (≤6 mg total 
dose for deflazacort) at ~6-week intervals can be considered. 
● 
If the severe behavioral problems continue to cause unacceptable disruption to 
school/ family life, corticosteroids may be stopped. See Section D below for 
procedures for withdrawal of corticosteroids. 
Bone Fractures Due to Osteoporosis 
Subjects who experience limb fractures should have fixation as directed by an orthopedic 
surgeon. Subjects who develop vertebral fractures can be treated with bisphosphanates 
(eg, pamidronate, 0.5 to 1 mg/kg/day IV for 3 days every 4 months). Subjects should not 
have a corticosteroid dosage adjustment due to the occurrence of fractures. 
Cataracts 
The development of cataracts should prompt referral to an ophthalmologist for evaluation. 
Subjects should not have a corticosteroid dosage adjustment due to the occurrence of 
cataracts. 

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Cushingoid Appearance 
If the subject develops a Cushingoid appearance, that is unacceptable to the subject/family, 
the following actions are recommended: 
● 
Corticosteroid dosage should not be increased to adjust for increases in body 
weight 
● 
Reassurance and support should be provided. Counseling from a child 
psychologist should be considered. 
● 
If the Cushingoid appearance remains unacceptable to child/family, dosage 
reductions of ≤5 mg total dose for prednisone (≤6 mg total dose for deflazacort) at 
~6-week intervals can be considered. 
● 
Every attempt should be made to avoid stopping corticosteroids solely for 
Cushingoid appearance; if the subject/family demands that corticosteroids be 
stopped, see Section D below for procedures for withdrawal of corticosteroids. 
Gastrointestinal Irritation 
In the event of the development of symptoms consistent with esophagitis, gastritis, or 
duodenitis, the following interventions are recommended: 
● 
Treatment with supportive care (H2 antagonists, proton pump inhibitors, antacids) 
should be initiated and corticosteroid dosage should not be increased to adjust for 
increases in body weight. 
● 
If symptoms persist for ≤6 weeks despite supportive care (H2 antagonists, proton 
pump inhibitors, antacids), a gastroenterology consultation should be obtained 
● 
If symptoms persist despite continued supportive care (H2 antagonists, proton 
pump inhibitors, antacids) and gastroenterology evaluation, dosage reductions of 
≤5 mg total dose for prednisone (≤6 mg total dose for deflazacort) at ~6-week 
intervals can be considered. 
● 
If the gastroenterologist recommends discontinuation of corticosteroids for frank 
gastrointestinal ulceration, bleeding, etc, corticosteroids may be stopped. See 
Section D below for procedures for withdrawal of corticosteroids. 
Height Gain Inhibition 
In the event of an inhibition of body height increases that is unacceptable to the 
subject/family, the following interventions are recommended: 
● 
Corticosteroid dosage should not be increased to adjust for increases in body 
weight 
● 
Reassurance and support should be provided. Counseling from a child 
psychologist should be considered. 
● 
If the failure to gain height remains unacceptable to child/family, dosage 
reductions of ≤5 mg total dose for prednisone (≤6 mg total dose for deflazacort) at 
~6-week intervals can be considered. 

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● 
Every attempt should be made to avoid stopping corticosteroids solely for failure 
to gain height; if the subject/family demands that corticosteroids be stopped, see 
Section D below for procedures for withdrawal of corticosteroids. 
Hyperglycemia or Glycosuria 
Evidence of fasting hyperglycemia or ≥1+ glycosuria persisting for ≥6 weeks should prompt 
the following interventions: 
● 
Institute monitoring of glycosylated hemoglobin (hemoglobin A1c) to evaluate for 
evidence of chronic hyperglycemia. 
● 
If hyperglycemia or glucosuria is only episodic and chronic hyperglycemia is not 
present by hemoglobin A1c, corticosteroids should not to be increased to adjust for 
increases in body weight. 
● 
If chronic hyperglycemia is present by hemoglobin A1c, consultation should be 
arranged with an endocrinologist regarding diagnostic evaluation and potential 
intervention for hyperglycemia 
● 
If hyperglycemia persists and corticosteroid dose reduction is warranted, dosage 
reductions of ≤5 mg total dose for prednisone (≤6 mg total dose for deflazacort) at 
~6-week intervals can be considered. 
● 
If the endocrinologist recommends corticosteroid discontinuation, corticosteroids 
may be stopped. See Section D below for procedures for withdrawal of 
corticosteroids. 
Hypertension 
Evidence of substantial hypertension (blood pressure elevation at 99th percentile + 15 mmHg 
for age) persisting for ≥6 weeks should prompt the following interventions: 
● 
Corticosteroids should not to be increased to adjust for increases in body weight. 
Dietary recommendations (weight reduction/sodium reduction) should be 
considered. 
● 
If substantial hypertension persists, appropriate blood pressure management 
(eg, diuretics, beta blockers, calcium channel blockers) can be considered. If they 
can be avoided, angiotensin converting enzyme inhibitors or angiotensin receptor 
blockers should not be instituted during study drug therapy because such drugs 
may elevate plasma renin values and obscure monitoring for potential ataluren 
hypoaldosteronism. 
● 
If hypertension persists despite continued antihypertensive therapy, dosage 
reductions of ≤5 mg total dose for prednisone (≤6 mg total dose for deflazacort) at 
~6-week intervals can be considered. 
● 
If hypertension persists despite continued antihypertensive support and 
corticosteroid dosage reductions, corticosteroids may be stopped. See Section D 
below for procedures for withdrawal of corticosteroids. 

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Infections Potentially Related to Corticosteroid-Mediated Immunosuppression 
Unusual opportunistic infections or unusual responses to infection potentially consistent with 
corticosteroid-mediated immunosuppression should prompt the following interventions: 
● 
Corticosteroids should not to be increased to adjust for increases in body weight 
and consultation with an infectious disease expert should be obtained. 
● 
If infections cannot be managed with appropriate antibiotic prophylaxis or 
treatment, dosage reductions of ≤5 mg total dose for prednisone (≤6 mg total dose 
for deflazacort) at ~6-week intervals can be considered. 
● 
If infections are clinically severe and/or persistent despite corticosteroid dosage 
reductions, corticosteroids may be stopped. See Section D below for procedures 
for withdrawal of corticosteroids. 
Weight Gain 
In the event of a body weight increase that is unacceptable to the subject/family, the 
following interventions are recommended: 
● 
Corticosteroid dosage should not be increased to adjust for increases in body 
weight 
● 
Reassurance and support should be provided. Counseling from a nutritionist 
should be considered. 
● 
If the body weight increase remains unacceptable to child/family, dosage 
reductions of ≤5 mg total dose for prednisone (≤6 mg total dose for deflazacort) at 
~6-week intervals can be considered. 
● 
Every attempt should be made to avoid stopping corticosteroids solely due to 
increase in weight; if the subject/family demands that corticosteroids be stopped, 
see Section D below for procedures for withdrawal of corticosteroids. 
D. 
Withdrawal of Corticosteroids 
Corticosteroids should not be stopped suddenly. A tapered reduction in dosage is required to 
avoid risks of adrenal insufficiency. Tapering of drug dosage should follow the normal 
clinical practice of taking ½ the regular dose for the first week, ¼ the regular dose for the 
second week, 1/8 the regular dose for the third week and no study drugs thereafter. All 
adverse effects possibly due to corticosteroid should be monitored until resolved and subjects 
should be followed closely for symptoms consistent with adrenal insufficiency. Subjects who 
require corticosteroid discontinuation may remain on blinded study drug therapy. 
E. 
Reinstitution of Corticosteroids 
In subjects who discontinue corticosteroids after following the recommended interventions 
and corticosteroid dosage modification procedures, reinstitution of corticosteroids is not 
generally recommended unless adrenal insufficiency is detected. However, if reinstitution of 
corticosteroids is deemed necessary, the corticosteroid dosage should be lower than the 
lowest total dose that previously proved intolerable. Subjects who require corticosteroid 
reinstitution may remain on blinded study drug therapy.