A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study With an Open-Label Extension to Determine the Safety, Pharmacokinetics and Efficacy of Oral Ifetroban in Subjects With Duchenne Muscular Dystrophy
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy Cardiomyopathy, Cardiomyopathy, Dilated
Sponsor: Cumberland Pharmaceuticals

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CLINICAL STUDY PROTOCOL 
 
A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study with 
an Open-Label Extension to Determine the Safety, Pharmacokinetics and 
Efficacy of Oral Ifetroban in Subjects with Duchenne Muscular Dystrophy 
 
Number: CPI-IFE-007 
 
Protocol Version 
 
Version Number:  
Original Protocol 
Final:  
 
08 December 2017 
 
Amendment:   
01 
Revised Final:  
01 October 2018 
 
Amendment:  
02 
Revised Final:  
29 July 2022 
 
Amendment:  
03 
Revised Final:  
06 June 2023 
 
Amendment:  
04 
Revised Final:  
29 July 2024 
 
Amendment:  
04a 
Revised Final:  
10 March 2025 
 
CONFIDENTIALITY STATEMENT 
The information in this document contains trade secrets and commercial information that are privileged or 
confidential and may not be disclosed unless such disclosure is required by applicable laws and regulations. 
In any event, persons to whom the information is disclosed must be informed that the information is 

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privileged or confidential and may not be further disclosed by them. These restrictions on disclosure will 
apply equally to all future information supplied to you which is indicated as privileged or confidential. 
RESPONSIBLE PERSONNEL  
Sponsor - Medically Responsible Person 
 Sponsor’s Coordinating Office 
 
  
Todd Rice, MD, MSc 
 Leo Pavliv, RPh 
Senior Director, Medical Affairs 
 Development and Operations Advisor 
Cumberland Pharmaceuticals Inc. 
 Cumberland Pharmaceuticals Inc. 
1600 West End Avenue, Suite 1300 
 1600 West End Avenue, Suite 1300 
Nashville, TN 37203 
 Nashville, TN 37203 
USA 
 USA 
 
  
Tel.: 
615-322-3412  
 Tel.: 
615-255-0068  
Fax.: 615-343-7448 
 Fax.: 866-438-2372 
 
 lpavliv@cumberlandpharma.com 
 
  
Sponsor’s Clinical Operations  
 Coordinating Investigator 
 
 
 
Ingrid Anderson, PhD, CCRP 
 Larry W. Markham, M.D. 
Senior Clinical Project Manager 
 Principal Investigator 
Cumberland Pharmaceuticals Inc. 
1600 West End Avenue, Suite 1300 
Nashville, TN 37203 
USA 
 
Tel.:    615-627-4121 
Fax:    866-438-2372 
ianderson@cumberlandpharma.com 
 Riley Hospital for Children 
705 Riley Hospital Drive, RR 127 
Indianapolis, Indiana 46202-5225 
USA 
 
Tel: (317) 944-8906 
lwmarkha@iu.edu 
 
  
 
  
 
  
 
  
 
  
 
  
 

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1 INVESTIGATOR’S STATEMENT 
I have read and agree to the Protocol CPI-IFE-007, Amendment 04: “A Randomized, Double-
Blind, Placebo-Controlled, Multiple Dose Study with an Open-Label Extension to Determine the 
Safety, Pharmacokinetics and Efficacy of Oral Ifetroban in Subjects with Duchenne Muscular 
Dystrophy, dated 10 March 2025.”  I am aware of my responsibilities as an Investigator under the 
guidelines of Good Clinical Practice (GCP), local regulations (as applicable) and the study 
protocol.  I agree to conduct the study according to these guidelines and to appropriately direct and 
assist the staff under my control, who will be involved in the study. 
 
 
 
Principal Investigator 
Signature: 
 
 
 
 
 
 
Date of Signature 
 
 
 
 
 
 
Sponsor Signature 
Signature: 
 
 
 
 
Todd Rice, MD, MSc 
 
Date of Signature 
 
Senior Director, Medical Affairs  
 
 
 
 
Signature: 
 
 
 
 
Leo Pavliv, RPh 
 
Date of Signature 
 
Development and Operations Advisor 

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2 SYNOPSIS 
Name of Sponsor: 
Cumberland Pharmaceuticals  
Name of Finished Product: 
Ifetroban Capsules 
Name of Active Ingredient: 
ifetroban 
Title of Study: 
A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study with an Open-Label 
Extension to Determine the Safety, Pharmacokinetics and Efficacy of Oral Ifetroban in Subjects 
with Duchenne Muscular Dystrophy 
Study Centers (Planned):  Ten 
Phase of Development:  II 
Expected Study Duration (per subject): Screening period (12 weeks) + Treatment period (12 
months) + Open-label Extension (repeatable periods of 12 months) 
Objectives: 
Primary Study Objective 
• Assess the safety of oral ifetroban in male subjects with Duchenne Muscular Dystrophy 
(DMD) 
Secondary Study Objectives 
• Evaluate the pharmacokinetics and efficacy of oral ifetroban. 
Exploratory Study Objectives 
• Evaluate novel biomarkers for diagnosis and monitoring of cardiomyopathy in DMD 
• Evaluate changes in daily life activity and quality of life 
Methodology: This is a randomized, double-blind, placebo-controlled, multiple dose study 
with an open-label extension to determine the safety, pharmacokinetics and efficacy of low or 
high doses of oral ifetroban compared to placebo in subjects with DMD. 
Number of subjects (planned):  A total of 48 DMD subjects will be enrolled: 24 subjects with 
early stage DMD (LVEF > 45%) and 24 with advance stage DMD (LVEF 35% - 45% or 
historically documented LVEF 35%-45% and baseline LVEF less than 50%) 
Study Population – Main Selection Criteria 
Inclusion criteria: 
1. Males 7 years of age and older with the diagnosis of DMD, defined as phenotype 
consistent with DMD and either positive genotype, first degree relative with positive 
genotype, or confirmatory muscle biopsy. 
2. Stable dose of oral corticosteroids for at least 8 weeks or has not received corticosteroids 
for at least 30 days. 
3. Stable cardiac function defined as change in left ventricular ejection fraction (LVEF) of 
< 15% and no heart failure admission over the last 12 months; LVEF 35% or greater by 
cine cardiac magnetic resonance imaging (MRI) or echocardiography; myocardial 
damage in one or more left ventricular segments evident by late gadolinium enhancement 
allowed; concurrent angiotensin-converting enzyme inhibitors (ACEI), beta-blocker (BB) 
or angiotensin receptor blocker (ARB) therapy allowed (selection of which dictated by 
clinical care) if started three months or greater from first dose of IMP without change in 
dose. Aldosterone receptor antagonists (eg. Spironolactone or eplerenone) allowed if 
started 12 months or greater from first dose of Investigational Medicinal Product (IMP). 
No changes throughout the study allowed, except in the event of a decline in left ventricular 
ejection fraction (LVEF) >5% following the baseline CMR as measured by a subsequent CMR 

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Name of Sponsor: 
Cumberland Pharmaceuticals  
Name of Finished Product: 
Ifetroban Capsules 
Name of Active Ingredient: 
ifetroban 
at the same center. Should this occur, changes in cardiac medications are allowed on the study. 
a. Late-stage cohort: Subjects are eligible for the late-stage cohort if the subject has: 
i. LVEF 35%-45% by cine cardiac magnetic resonance imaging (MRI) or 
echocardiography or  
ii. historically documented LVEF 35%-45% by cine cardiac magnetic resonance 
imaging (MRI) or echocardiography and if their baseline MRI is less than 50%. 
4. Subjects aged 18 years and older, informed consent obtained directly. For subjects ages 
7–17 years old (yo), both assent from the subject and permission from a parent or 
guardian.  
5. AAV-based gene therapy permitted if ≥ 2 years from AAV administration and subject has 
documented cardiac decline defined as >5% decline in LVEF over a 2-year period 
following AAV administration using consecutive CMRs or echocardiography performed 
at the same center (must still meet inclusion criterion #3). 
Exclusion criteria: 
1. Clinically significant illness other than DMD 
2. Clinically significant laboratory abnormality not associated with DMD 
3. Major surgery within six weeks prior to the first dose of study drug, or planned surgery 
during this study which would interfere with the ability to perform study procedures 
4. Require antiarrhythmic therapy and/or initiation of diuretic therapy for management of 
acute heart failure in the last 6 months  
5. A LVEF of < 35% by CMR and/or fractional shortening of < 15% based on ECHO 
during screening 
6. A known bleeding disorder or has received anticoagulant treatment within 2 weeks of 
study entry 
7. Allergy to gadolinium contrast or known renal insufficiency defined as abnormal 
cystatin C or creatinine above the upper limit of normal for age. The male serum 
reference ranges as follows: 
8. Age 7-9 years - 0.2-0.6 mg/dL 
9. Age 10-11 years - 0.3-0.7 mg/dL 
10. Age 12-13 years - 0.4-0.8 mg/dL 
11. Age 14-15 years - 0.5-0.9 mg/dL 
12. Age 16 years or older - 0.8-1.3 mg/dL 
13. Non-MR compatible implants (e.g. neurostimulator, automatic implantable 
cardioverter-defibrillator [AICD]) 
14. Subjects who participated in a therapeutic clinical trial within 30 days or five half-lives 
(whichever is longer) of study entry  
15. Any other condition that could interfere with the subject’s participation 
Investigational Medicinal Product (IMP), dose and mode of administration: 
Oral ifetroban capsules, Doses:  
Low Dose:  < 35 kg: 50 mg, ≥ 35 kg: 100 mg/day 
High Dose: < 35 kg: 150 mg, ≥ 35 kg: 300 mg/day 
Matching oral placebo capsules 
Duration of treatment: Twelve months 

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Name of Sponsor: 
Cumberland Pharmaceuticals  
Name of Finished Product: 
Ifetroban Capsules 
Name of Active Ingredient: 
ifetroban 
Endpoints: 
Primary Endpoint: 
Safety and tolerability (baseline to 12 months): percentage of subjects with one or more treatment 
emergent adverse event (TEAE) 
 
Secondary Endpoints: 
• Pharmacokinetics – Peak plasma concentration of ifetroban after administration and its acyl 
glucuronide metabolite. Time of Cmax (Tmax), AUC, Clearance and Elimination half-life 
(t1/2). Dot blots of blood will be collected pre-dose and post-dose at 30, 60 (±5) minutes; 4, 
8 and 24 hours (all ± 30 minutes) on Day 0 (first dose) and pre-dose and at 30 minutes (±5) 
post dose on Day 7 (steady-state). 
• Efficacy of ifetroban over 12 months of dosing  
o Change from baseline in LVEF using cardiac MRI (CMR);  
o Change from baseline in myocardial strain using CMR;  
o Change from baseline in Pulmonary function test results including peak expiratory flow 
(PEF), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), 
maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP);  
o Change from baseline in Pediatric Quality of Life Inventory (PedsQL) results, including 
the gastrointestinal (GI) module and neuromuscular module (NMM) 
 
Exploratory Endpoints: 
• Novel biomarkers for diagnosis and monitoring of cardiomyopathy in DMD including 
but not limited to change from baseline in miRNAs, eicosanoids, claudin-5, CD49d, CPK, 
hs-Trop, NT-proBNP and structural cardiac magnetic resonance (CMR) results 
• Change from baseline in daily life activity to evaluate motor function and estimate muscle 
strength measured by an actigraphy sensor worn for 1 week at baseline, Month 6 and 
Month 12. 
• 
Change from baseline in Quantitative Muscle Testing (QMT) to assess muscle strength 
Sample Size: 
The sample size is based on the comparison of each dose level of ifetroban (Low Dose or High 
Dose) to placebo with respect to change from baseline in LVEF using CMR for each disease 
stage, early (LVEF > 45%) or advanced (current/historical LVEF 35% - 45%). Assuming 
observations from each treatment group have normal distributions with an effect size of 1.6 for 
the comparison of a dose of ifetroban to placebo, 8 subjects for each treatment group within 
disease stage will provide power exceeding 85% for a t-test at two-sided level 0.05. Under these 
assumptions, 8 subjects for each treatment group within disease stage will provide power 
exceeding 80% for the Wilcoxon rank sum test at two-sided level 0.05. A total of 48 DMD 
subjects will be enrolled: 24 subjects with early stage DMD (LVEF > 45%) and 24 with advance 
stage DMD (current/historical LVEF 35%-45%). Assuming a dropout rate of 25%, 60 subjects 
will be recruited to meet the target sample size of 48 subjects. 
 
 

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Name of Sponsor: 
Cumberland Pharmaceuticals  
Name of Finished Product: 
Ifetroban Capsules 
Name of Active Ingredient: 
ifetroban 
Enrollment: 
Subjects will be randomly assigned to one of three oral treatment groups: low-dose ifetroban, 
high-dose ifetroban or placebo for 12 months based on weight within each disease stage, early 
(LVEF > 45%) or advance (current/historical LVEF 35%-45%).  
Low Dose:  < 35 kg: 50 mg, ≥ 35 kg: 100 mg/day  
High Dose: < 35 kg: 150 mg, ≥ 35 kg: 300 mg/day 
 
Analysis Population: 
All subjects who receive at least one dose of study medication will be included in the Safety 
Population. All safety data will be summarized for subjects in the Safety Population. 
 
The Intent-To-Treat (ITT) Population will consist of all treated subjects with at least one post-
baseline assessment. The Per Protocol (PP) Population will consist of all subjects in the ITT 
population with no major protocol violations, including violation of inclusion or exclusion 
criteria or insufficient dosing where the latter includes missing more than 2 consecutive weeks 
of dosing for any reason or missing >20% of prescribed doses between visits. Summary statistics 
will be presented for both the ITT and PP Populations.  
 
Interim Analysis: 
An early analysis will be performed when half the target enrollment has completed the six month 
visit and assessments. Key findings for the interim analysis will be summarized. 
 
Historical Comparator Analyses: 
Endpoints collected during both the double-blind and open label portions of the study will be 
compared with a U.S. Food and Drug Administration (FDA)-funded DMD natural history study 
(NHS) with similar endpoint design and yearly study visits. NHS data from patients matched by 
age, baseline LVEF, and background DMD therapy to CPI-IFE-007 study subjects will be used 
to supplement the placebo arm of the double-blind portion of the study and will be used as the 
primary comparator for data collected during the open-label extension.  
 
 

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3 TABLE OF CONTENTS 
1 
INVESTIGATOR’S STATEMENT ............................................................................. 3 
2 
SYNOPSIS .................................................................................................................. 4 
3 
TABLE OF CONTENTS ............................................................................................. 8 
List of Tables 11 
List of Figures ................................................................................................................................11 
4 
LIST OF ABBREVIATIONS .................................................................................... 12 
5 
INTRODUCTION ..................................................................................................... 15 
5.1 
Background Information ....................................................................................... 15 
5.1.1 
Duchenne Muscular Dystrophy ......................................................................... 15 
5.1.2 
Ifetroban............................................................................................................. 16 
5.2 
Stage of Development ........................................................................................... 20 
5.3 
Trial Rationale ....................................................................................................... 20 
5.4 
Dose Rationale ....................................................................................................... 20 
5.5 
Risk-Benefit Assessment ....................................................................................... 21 
6 
STUDY OBJECTIVES & ENDPOINTS .................................................................. 21 
6.1 
Primary Objective .................................................................................................. 21 
6.2 
Secondary Objectives ............................................................................................ 21 
6.3 
Exploratory Objectives .......................................................................................... 21 
6.4 
Primary Endpoint ................................................................................................... 21 
6.5 
Secondary Endpoints ............................................................................................. 21 
6.6 
Exploratory Endpoints ........................................................................................... 22 
7 
STUDY DESCRIPTION ........................................................................................... 23 
7.1 
Study Design ......................................................................................................... 23 
7.1.1 
Pharmacokinetics ............................................................................................... 24 
7.2 
Drugs and Dosages ................................................................................................ 25 
7.3 
Selection of Study Population ............................................................................... 26 
7.3.1 
Inclusion Criteria ............................................................................................... 26 
7.3.2 
Exclusion Criteria .............................................................................................. 27 
7.4 
Concomitant Medications ...................................................................................... 28 
7.5 
Prohibited Medications and Procedures ................................................................ 29 

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7.6 
Dietary Requirements ............................................................................................ 29 
8 
STUDY VISITS AND PROCEDURES .................................................................... 30 
8.1 
Overview – Schedule of Time and Events ............................................................ 30 
8.1.1 
Screening Period ................................................................................................ 30 
8.1.2 
Treatment Period ............................................................................................... 32 
8.1.3 
Optional Open-Label Extension ........................................................................ 35 
9 
SUBJECT DISCONTINUATION AND STUDY OR SITE TERMINATION ......... 40 
9.1 
Subject Discontinuation ......................................................................................... 40 
9.2 
Study or Site Termination ...................................................................................... 40 
10 
ADVERSE EVENTS................................................................................................. 41 
10.1 
Definitions ............................................................................................................. 41 
10.1.1 
Adverse Event Definitions ................................................................................ 41 
10.1.2 
Adverse Event Assessment Definitions ............................................................. 42 
10.2 
Collection, Recording and Reporting of Adverse Events ...................................... 43 
10.3 
Follow-up of Adverse Events ................................................................................ 44 
11 
STATISTICAL METHODS AND DATA ANALYSIS .............................................. 44 
11.1 
Sample Size Determination ................................................................................... 44 
11.2 
Subject Populations for Analysis ........................................................................... 45 
11.2.1 
Safety Population ............................................................................................... 45 
11.2.2 
Intent-to-Treat Population ................................................................................. 45 
11.2.3 
Per Protocol Population ..................................................................................... 45 
11.3 
Subgroup analysis .................................................................................................. 45 
11.4 
Interim Analysis ..................................................................................................... 45 
11.5 
Historical Comparator ........................................................................................... 46 
11.6 
Randomization ....................................................................................................... 46 
11.7 
Methods for Handling Missing Data ..................................................................... 47 
11.8 
Data Analysis Plan ................................................................................................. 47 
11.8.1 
Demographic and Baseline Characteristics ....................................................... 47 
11.8.2 
Exposure and Compliance ................................................................................. 47 
11.8.3 
Efficacy Analyses .............................................................................................. 47 
11.8.4 
Safety Parameters .............................................................................................. 48 
11.8.5 
PK Analysis ....................................................................................................... 48 
11.8.6 
Long-Term Safety and Efficacy Analyses ......................................................... 48 
12 
STUDY MANAGEMENT AND DATA COLLECTION .......................................... 49 

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12.1 
Confidentiality ....................................................................................................... 49 
12.2 
Source Documents ................................................................................................. 49 
12.3 
Case Report Forms ................................................................................................ 49 
12.4 
Records Retention ................................................................................................. 50 
13 
STUDY MONITORING, AUDITING, AND INSPECTING ................................... 50 
13.1 
Study Monitoring Plan .......................................................................................... 50 
14 
ETHICAL CONSIDERATIONS ............................................................................... 51 
14.1 
Informed Consent .................................................................................................. 51 
14.2 
Protocol Compliance ............................................................................................. 51 
14.3 
Study Files ............................................................................................................. 52 
15 
REFERENCES .......................................................................................................... 52 
16 
APPENDICES ........................................................................................................... 56 
16.1 
Protection of Human Subjects ............................................................................... 56 
16.1.1 
Basic Elements Of Informed Consent ............................................................... 56 
16.2 
Requisite Documents for Approval of Study Site ................................................. 58 
16.3 
Responsibilities and Obligations of Investigators and Sponsors ........................... 59 
16.3.1 
Sponsor/Study Monitor ..................................................................................... 59 
16.3.2 
Investigator ........................................................................................................ 60 
 
 
 

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List of Tables 
Table 7-1 Ifetroban Dose Levels & Sub-Groups .......................................................................... 25 
Table 8-1 
Schedule of Treatment & Events .......................................................................... 39 
 
List of Figures 
Figure 5-1  Ifetroban decreases RV fibrosis and improves cardiac function ................................ 17 
Figure 5-2  Ifetroban reduces LV fibrosis, improves cardiac function & survival in DMD ......... 19 
Figure 7-1 Study Design ............................................................................................................... 24 
 
 
 

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4 LIST OF ABBREVIATIONS  
Term 
Definition 
AAV 
Adeno-Associated Virus 
ACEI 
Angiotensin-converting enzyme inhibitors 
AE 
Adverse Event/Experience 
AICD 
Automatic implantable cardioverter-defibrillator 
ARB 
Angiotensin receptor blocker 
ARNI 
Angiotensin receptor/neprilysin inhibitor 
ASA 
ASO 
Acetylsalicylic acid 
Antisense oligonucleotide 
AUC 
Area Under the Curve 
BB 
Beta blocker 
C 
Celsius 
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
CI 
Contractility index 
CK 
Creatine kinase 
cm 
Centimeter 
Cmax 
Maximum Plasma Concentration 
CMP 
Comprehensive metabolic panel 
CMR 
Cardiac Magnetic Resonance  
COX 
Cyclooxygenase 
CPK 
Creatine Phosphokinase 
CRF 
Case Report Form 
CPI 
Cumberland Pharmaceuticals Inc. 
DKO 
Double Knockout 
DMD 
Duchenne Muscular Dystrophy 
dSG KO 
Delta-sarcoglycan knockout 
E/A 
early (E) to late (A) ventricular filling velocities 
ECHO 
echocardiography 
eCRF 
Electronic case report form 
EF 
Ejection fraction 
F 
Fahrenheit 
FDA 
Food and Drug Administration 
FEV1 
Forced Expiratory Volume in 1 Second 
FS 
Fractional shortening 

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Term 
Definition 
FVC 
Forced vital capacity 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
ICH 
International Conference on Harmonization  
IEC 
Independent Ethics Committee 
ife 
Ifetroban 
IMP 
Investigational Medicinal Product; synonymous with “study drug” 
INR 
International normalized ratio 
IRB 
ITT 
kg 
KO 
L 
Institutional Review Board 
Intent-To-Treat 
Kilogram 
Knockout 
Liter 
LGE 
Late gadolinium enhancement 
LGMD 
Limb-Girdle Muscular Dystrophy 
LVEF 
Left ventricle ejection fraction 
MedDRA 
Medical Dictionary for Regulatory Activities  
MEP 
Maximum expiratory pressure 
mg 
Milligram 
MIP 
Maximum inspiratory pressure 
mL 
Milliliter 
MRI 
Magnetic Resonance Imaging 
ng 
Nanogram 
NHS 
Natural history study 
NMM 
Neuromuscular Module 
Non-MR 
Non-magnetic resonance 
PAB 
Pulmonary arterial banding 
PAH 
Pulmonary arterial hypertension 
PedsQL 
Pediatric Quality of Life Inventory 
PEF 
Peak expiratory flow 
PFT 
Pulmonary Function Test 
PK 
Pharmacokinetic 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
QMT 
Quantitative Muscle Testing 

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Term 
Definition 
RV 
Right ventricle 
SAE 
Serious Adverse Event/Experience 
SGLT2 
Sodium glucose cotransporter-2 
SOC 
System Organ Class 
t1/2 
Half-life 
TEAE 
Treatment Emergent Adverse Event 
Tmax 
Time of maximum plasma concentration 
TPr 
Thromboxane Prostanoid Receptor 
TXA2 
Thromboxane A2 
TXAS 
Ves 
yo 
Thromboxane A2 Synthase 
End systolic volume 
years old 

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5 INTRODUCTION 
This study is to be performed in accordance with the International Conference on Harmonization’s 
(ICH) E6 guideline for Good Clinical Practice (GCP), the ethical principles that have their origin 
in the Declaration of Helsinki, and Title 21 of the Code of Federal Regulations (CFR) Parts 50, 56 
and 312. 
5.1 
Background Information 
5.1.1 
Duchenne Muscular Dystrophy 
Duchenne muscular dystrophy (DMD) affects approximately one of every 3,300 male births 
worldwide (Quinlivan 2009) and is caused by the complete absence of the sarcolemmal protein 
dystrophin as a result of anomalies in the X-linked DMD gene. Loss of dystrophin leads to 
inexorable damage to skeletal and cardiac muscle, with cardiomyopathy increasingly recognized 
as a major cause of death (Romfh 2010). Due to ongoing muscle damage, patients with DMD have 
markedly elevated serum levels of the muscle protein creatine kinase (CK), which may be 10× to 
over 100× the normal limit, and an elevated CK level is a diagnostic sign (Konagaya 1986). There 
is currently no cure for DMD. Current treatment is limited to the management of symptoms which 
is fueling investigations aimed at targeting the genetic defect. Several therapies are in various 
stages of development, including utrophin up-regulation, stop codon read-through therapy, viral 
gene therapy, cell-based therapy and exon skipping. These have mainly focused on improving 
skeletal muscle function without addressing the cardiac aspects of the disease, which may 
aggravate cardiomyopathy. For this reason, preclinical and clinical focus on improving heart 
function is essential. 
The absence of dystrophin in the heart renders cardiomyocytes more sensitive to stretch-induced 
damage. This results in increased levels of intracellular calcium, thereby activating calpains and 
proteases that consequently degrade contractile proteins, promoting cellular death and fibrosis, all 
contributing to the development of cardiomyopathy (D’Amario 2017; van Westering 2015). 
Animal and human data demonstrate the myocardial damage is evident before functional decline 
such as a reduction in left ventricular ejection fraction (LVEF) (Rafael-Fortney 2016), endorsing 
a strategic treatment window for initiating cardioprotective treatment at earlier stages of 
myocardial disease while EF is preserved. LV systolic strain measured by cardiac magnetic 
resonance imaging (CMR) is a more sensitive measure of cardiac function, has high reproducibility 
(Soslow 2016) – a critical feature when testing hypotheses in patients with rare diseases to support 
efficient sample size reductions – and is abnormal in even the youngest boys with DMD well 
before EF drops (Hor 2009). Eplerenone was recently shown using CMR to attenuate the decline 

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of cardiac function compared to placebo (Raman 2015). The benefit was greater at an early stage 
of cardiac involvement. 
5.1.2 
Ifetroban 
Ifetroban is a new chemical entity under development by Cumberland Pharmaceuticals Inc. (CPI) 
for Duchenne Muscular Dystrophy (DMD) and other diseases. The current formulation of oral 
ifetroban is a 50 mg capsule. Ifetroban is a well characterized pharmacological antagonist of the 
thromboxane prostanoid receptor (TPr), and has been studied previously in healthy volunteers and 
subjects with cardiovascular diseases. CPI studied the safety of the intravenous formulation of 
ifetroban in subjects with hepatorenal syndrome and portal hypertension. The oral formulation of 
ifetroban is under phase 2 investigation in patients with aspirin exacerbated respiratory disease, 
portal hypertension and systemic sclerosis. A large safety database exists from this work in 
addition to the many ifetroban clinical studies conducted by Bristol-Myers Squibb.  
Thromboxane A2 (TXA2) is a member of the prostanoid family of arachidonic acid metabolites 
generated by the sequential action of three enzymes – phospholipase A2, cyclooxygenase (COX)-
1 or COX-2 and TXA2 synthase (TXAS). TXA2 directs multiple biological processes via its cell 
surface receptor, the TPr. The biosynthesis of TXA2 as well as isoprostanes, nonenzymatic free 
radical-derived products of arachidonic acid that can activate the TPr in vivo (Audoly 2000), is 
elevated in numerous cardiovascular and inflammatory diseases, as is expression of the receptor 
itself (Katugampola 2001). TXA2 has been widely implicated in a range of cardiovascular 
diseases, owing to its acute and chronic effects in promoting platelet aggregation, vasoconstriction, 
and proliferation (Smyth 2010).  
The G protein-coupled TPr, expressed in platelets, immune cells, smooth muscle, and 
cardiomyocytes, has deleterious consequences of activation in the heart that mirrors the fibrosis 
and calcium alterations associated with MD cardiomyopathy. TPr activation contributes to LV 
hypertrophy and heart failure in mouse models of systemic hypertension and Gh-overexpression 
(Francois 2004; Francois 2008; Zhang 2003). The best-characterized signaling pathway of the TPr 
is via Gq (Huang 2004; Kinsella 1997), and results in phospholipase C activation, calcium 
mobilization via intracellular stores, and protein kinase C activation. In ventricular 
cardiomyocytes, TPr activation causes increased intracellular calcium, arrhythmia, and cell death 
in ventricular cardiomyocytes (Wacker 2009), and administration of a TPr agonist induces 
ventricular arrhythmias in rabbits (Wacker 2006). Activation of the TPr is pro-fibrotic in multiple 
systems (Acquaviva 2013; Comporti 2008; Gelosa 2011), and we have recently shown that TPr 
antagonism dramatically decreases right ventricular fibrosis and improves cardiac function in a 
pressure-overload model of pulmonary arterial hypertension (West 2016). These studies also 

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demonstrated the cardioprotective effects of ifetroban were not duplicated by inhibiting 
cyclooxygenases with aspirin or by blocking TXA2 production with a thromboxane synthase 
inhibitor, ozagrel (Figure 5-1). These findings suggest TPr blockade by ifetroban may have a 
durable benefit on preserving cardiac function in subjects with DMD. Furthermore, available TPr 
is likely to be activated during DMD. Isoprostanes formed during oxidative stress and known to 
cause fibrosis through the receptor (Acquaviva 2013; Comporti 2008), is increased in both BMD 
and DMD patients (Grotto 2008), as well as in heart failure patients (Cracowski 2000). Thus, 
although the role of the TPr in DMD has not previously been studied, the ligand availability and 
known signaling actions position the receptor to impact cardiomyopathy and the decline of cardiac 
function in DMD, where it may be an important therapeutic target. 
Figure 5-1  Ifetroban decreases RV fibrosis and improves cardiac function 
 
Antagonism of the TPr with ifetroban, but not inhibition of cyclooxygenase (aspirin; ASA) or thromboxane synthase 
(ozagrel; oza), decreases RV fibrosis 2 weeks after pulmonary arterial banding (PAB; A-B). Ifetroban treatment also 
improved RV contractility index (CI) and normalized stiffness (Tau) and end systolic volume (Ves) at 3 weeks post-
PAB (C; n=7-14), and prevented the decrease in fractional shortening at 6 weeks post-PAB (D). *, p<0.05, **, p<0.01 
by one-way ANOVA/Sidek’s posttest. Source: West 2016 
 
 
Recently, the effects of long-term antagonism of the TPr on the development of fibrosis and 
cardiomyopathy associated with muscular dystrophy were investigated. Treatment with ifetroban 
increased animal survival and improved the cardiac phenotype in three different murine models of 
MD (Figure 5-2): the δ-sarcoglycan knockout (dSG KO) mouse model of Limb-Girdle Muscular 
Dystrophy (LGMD); utrophin/dystrophin double knockout (DKO) mice and mdx/mTR mice, two 
models of severe DMD. TPr antagonism improved cardiac output in two models of severe DMD, 
and increased ejection fraction while decreasing cardiac fibrosis, TGFβ signaling, and expression 

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of matricellular genes in LGMD mice. In dSG KO LGMD mice, the normalized ejection fraction 
reflected improved diastolic filling, via decreased fibrosis and corrected calcium decay and 
cardiomyocyte relaxation, compared with vehicle-treated mice. Ifetroban helped to increase 
expression of claudin-5 and nNOS protein, which have also been shown to improve cardiac 
function in DMD (Lai 2014), and normalized expression of select genes typically upregulated in 
DMD (West 2018). Altogether, these results suggest that the TPr is activated in DMD and 
contributes to the cardiac phenotype. The inhibition of LV fibrosis and dysfunction by ifetroban is 
encouraging as LV dilation and the development of depressed LVEF are common findings in 
subjects with DMD and often present in the second decade of life. DMD subjects assessed using 
late gadolinium enhancement (LGE) by CMR demonstrated progressive myocardial fibrosis in the 
LV that was found to increase with age and correlate with a decline in LVEF (Tandon 2015). This 
preclinical evidence provides the medical rationale in this current study, which aims to test the 
hypothesis oral ifetroban may have a cardioprotective effect in DMD. 

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Figure 5-2  Ifetroban reduces LV fibrosis, improves cardiac function & survival in DMD 
 
Treatment with the TPr antagonist ifetroban (ife) improves survival (A), normalizes fractional shortening (FS) and ejection fraction (B) and decreases epicardial 
interstitial fibrosis (C; n=4-5) in dSG KO LGMD male mice. Fibrotic area was quantified from trichrome-stained slices in Leica Image Analysis using the same 
trichrome-defined image mask for all slides. Ifetroban also decreased phospho-SMAD2/3, a TGFβ signaling molecule (E; n=2). Comparisons by unpaired t-tests 
shown; intervening lanes were removed from blot in E. Utrophin-dystrophin double knockout DMD mice (DKO) and dystrophin KO mice with short telomeres 
(G2 mdx/mTR) have increased survival (E, G) and improved LV cardiac index with ifetroban treatment (F, H). The results of log-rank test (E, G) or unpaired t-
test (F, H) comparisons are shown. (H) is male mice only, due to sex differences of cardiac output in fully grown mice.*, p<0.05 by log-rank test. dSG KO=delta-
sarcoglycan knockout. 
Source: West 2019 
 
 

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5.2 
Stage of Development  
CPI-IFE-007 is randomized, double-blind, placebo-controlled, multiple dose study with an open-
label extension to determine the safety, pharmacokinetics and efficacy of two dose ranges of oral 
ifetroban in subjects with DMD.  
Approximately 48 subjects will be randomly assigned to one of three treatment groups for 12 
months of treatment: low-dose ifetroban, high-dose ifetroban or matching placebo, with 24 
subjects within each disease stage, early (LVEF > 45%) or advance (current/historical LVEF 35%-
45%). Patients who complete 12 months of treatment are eligible to participate in a repeatable 
open-label extension period of 12 months. 
5.3 
Trial Rationale 
The current trial is based on preliminary data which evaluated ifetroban using preclinical models 
of PAH and DMD to prevent cardiac fibrosis and dysfunction. Blockade of the TPr with ifetroban 
dramatically decreased right ventricular fibrosis and improved cardiac function in a pressure-
overload model of PAH (West 2016; Figure 5-1). Aside from the right ventricle, TPr antagonism 
with ifetroban decreased LV cardiac fibrosis and improved cardiac function and survival in animal 
models of LGMD and DMD (Figure 5-2). Ifetroban also normalized plasma levels of troponin I, a 
biomarker for cardiac injury, and decreased cardiac expression of the atrial and brain natriuretic 
peptides, clinical biomarkers of cardiac dysfunction (not shown). These results provide the medical 
rationale to study ifetroban as a potential novel treatment for DMD. CPI-IFE-007 is a safety study 
designed to investigate the pharmacokinetics and efficacy of two oral dose ranges of ifetroban 
compared to placebo, to treat cardiac dysfunction in DMD subjects. The current study design will 
leverage data from an FDA-funded DMD CM natural history study with identical CMR protocol, 
endpoints and procedures to supplement our analysis. This strategy will enhance statistical power 
and strengthen our comparator arm through the inclusion of additional matched control subjects. 
5.4 
Dose Rationale 
Oral ifetroban doses ≥ 100 mg have been shown to inhibit TPr induced platelet aggregation, with 
corresponding plasma Cmax levels of > 500 ng/mL. The bioavailability of oral ifetroban capsules 
has previously been found to be ≈ 42%. Our multi-dose safety studies have found oral ifetroban at 
up to 500 mg daily to be safe and well tolerated however these studies did not include children. 
For this reason, this study aims to compare two dose ranges of oral ifetroban (a low dose and high 
dose based on weight) to placebo for at least twelve months. A placebo treatment arm is included 
to help provide data on the natural history of the disease. 

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5.5 
Risk-Benefit Assessment 
Ifetroban prevents TPr ligand binding and activation which plays a role in oxidative stress, 
isoprostane generation, smooth muscle contraction and inflammation. Ifetroban has been studied 
in over 26 clinical studies and evaluated for safety in over 1,400 subjects. Most of these studies 
were conducted in subjects with cardiovascular disease. A large safety database from this work has 
shown no safety concerns with the use of ifetroban at doses as high as 500 mg daily. Based upon 
the current available data for ifetroban and the review of the data by an independent data 
monitoring committee, no important identified risks have been established. There is a potential 
risk based on the mechanism of action that treatment with a TPr antagonist may inhibit platelet 
function and thereby increase the risk of bleeding  however multi-dose safety studies have not 
demonstrated an increased risk of bleeding with ifetroban. Although our clinical studies have not 
demonstrated abnormal laboratory findings or bleeding events as a safety concern, clinical 
laboratory results will be closely monitored for possible abnormalities related to clotting or 
bleeding in all study subjects.  
Given the preclinical data, there is a potential survival benefit to study subjects treated with 
ifetroban. If TPr antagonism does indeed provide cardiac symptom control and improve the cardiac 
function for subjects with DMD, it would support the use of ifetroban as a therapeutic agent. As 
such, the potential risk to subjects seems reasonable compared to the potential benefit. 
6 STUDY OBJECTIVES & ENDPOINTS 
6.1 
Primary Objective 
Assess the safety of oral ifetroban in male subjects with Duchenne Muscular Dystrophy (DMD). 
6.2 
Secondary Objectives 
Evaluate the pharmacokinetics and efficacy of oral ifetroban in DMD subjects. 
6.3 
Exploratory Objectives 
Evaluate novel biomarkers for diagnosis and monitoring of cardiomyopathy in DMD. 
6.4 
Primary Endpoint 
Safety and tolerability (baseline to 12 months): percentage of subjects with one or more treatment 
emergent adverse events (TEAE) . 
6.5 
Secondary Endpoints 
• Pharmacokinetics (PK) – Peak plasma concentration of ifetroban after administration and 
its acyl glucuronide metabolite (Cmax). Time of Cmax (Tmax), AUC, Clearance and 

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Elimination half-life (t1/2). Blood samples will be collected pre-dose for all subjects and 
at 30, 60 (±5) minutes; and 4, 8 and 24 hours (all ± 30 minutes) post dose on Day 0 (first 
dose) and pre-dose and 30 minutes post-dose at Day 7 (steady-state). 
• Efficacy of ifetroban over 12 months of dosing  
− Change from baseline in LVEF using CMR;  
− Change from baseline in myocardial strain using CMR;  
− Change from baseline in Pulmonary function test results including peak expiratory 
flow (PEF), forced vital capacity (FVC), forced expiratory volume in 1 second 
(FEV1), maximum inspiratory pressure (MIP), and maximum expiratory pressure 
(MEP);  
− Change from baseline in Pediatric Quality of Life Inventory (PedsQL) results, 
including the gastrointestinal (GI) module and neuromuscular module (NMM). 
• Efficacy of ifetroban over 24 to 36 months of dosing (for the open label population) 
− Change from baseline or Month 12 in LVEF using CMR;  
− Change from baseline or Month 12 in myocardial strain using CMR;  
− Change from baseline or Month 12 in Pulmonary function test results including 
peak expiratory flow (PEF), forced vital capacity (FVC), forced expiratory volume 
in 1 second (FEV1), maximum inspiratory pressure (MIP), and maximum 
expiratory pressure (MEP);  
6.6 
Exploratory Endpoints 
• Novel biomarkers for diagnosis and monitoring of cardiomyopathy in DMD including but 
not limited to change from baseline in miRNAs, eicosanoids, claudin-5, CD49d, CPK, hs-
Trop, NT-proBNP and structural CMR results 
• Change from baseline in daily life activity to evaluate motor function and estimate muscle 
strength measured by an actigraphy sensor worn for one week at baseline, Month 6 and 
Month 12; Change from baseline and Month 12 in daily activity at Month 24 or Month 36⸷ 
for the open label population. 
• Change from baseline in Quantitative Muscle Testing (QMT) to assess muscle strength; 
Change from baseline and Month 12 in QMT at Month 24 or Month 36⸷ for the open label 
population. 
⸷ Note: Change from baseline and Month 12 at Month 36 will only be evaluated for patients 
who completed these endpoint measurements prior to CPI-IFE-007 Protocol Amendment 04a. 

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7 STUDY DESCRIPTION 
7.1 
Study Design 
CPI-IFE-007 is double-blind, placebo-controlled, multicenter, dose-ranging study with an open-
label extension to determine the safety, pharmacokinetics and efficacy of two dose ranges of oral 
ifetroban in subjects with DMD. DMD patients who meet the inclusion criteria and none of the 
exclusion criteria will receive oral Investigational Medicinal Product (IMP) once daily for 12 
months. Subjects will be randomly assigned to one of three treatment groups, low-dose ifetroban, 
high-dose ifetroban or placebo, and dosed based on weight. Each treatment group will be evaluated 
by eight subjects with early stage (LVEF > 45%) and eight subjects with advance stage 
(historical/current LVEF 35% - 45%) DMD for at least six months and a maximum of 12 months. 
Subjects who complete 12 months of treatment will be eligible to participate in repeatable open-
label extension periods of 12 months. An additional comparator group will be utilized from DMD 
patients evaluated in an FDA-funded natural history study (NHS) over multiple years matched to 
CPI-IFE-007 subjects by baseline LVEF, age, and background DMD therapy (Soslow 2023). The 
CPI-IFE-007 study is designed to mirror the FDA-funded DMD NHS in terms of procedures, 
imaging protocol, and endpoint assessments to enable valid comparisons between study 
populations. This design feature will facilitate the planned supplementation of the placebo arm 
with matched historical controls. All subjects who receive IMP will be assessed for safety. All 
subjects with at least one efficacy assessment post-baseline will be evaluated for efficacy. Blood 
and urine will be collected for standard and novel cardiac biomarkers.  
The double-blind study will be conducted with two periods: a screening period of up to 12 weeks 
and a treatment period of up to 12 months. The open label study consisting of high-dose ifetroban 
treatment will be conducted in repeatable periods of 12 months.  
 
 
 
 
 
 

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Figure 7-1 Study Design 
 
CBC = complete blood count; CMP = comprehensive metabolic panel; Coags = coagulation factors; 
ECG=electrocardiogram, Echo= echocardiography; QMT= quantitative muscle testing; PFT= pulmonary function 
test; QoL = quality of life; LVEF = left ventricle ejection fraction; CMR=cardiac MRI; PE = physical exam with 
vitals; PK=pharmacokinetics; W= week, M=month 
 
The total duration of the study participation for each subject is up to 52 weeks. There is a repeatable 
optional open-label extension period where any subject completing 12 months of treatment is 
eligible to participate. Recruitment is planned to stop when approximately 48 subjects have 
completed 12 months of treatment. The end of the study is defined as the last subject’s last 
visit/contact. 
7.1.1 
Pharmacokinetics 
Pharmacokinetic parameters, including peak plasma concentration of ifetroban after 
administration and its acyl glucuronide metabolite, Tmax, AUC, Clearance and t1/2, will be 
determined from analysis of collected blood drop samples (Section 11.7.5) using an auto-lancet 
and dry plasma prep cards. Blood samples (two drops of blood) for PK analysis will be collected 
at specified times on all subjects.  
PK samples (two drops of blood) will be collected on all subjects pre-dose and at 30, 60 (±5) 
minutes, 4, 8 and 24 hours (all ± 30 minutes) following the first dose of oral IMP and at steady-
state at Day 7 pre-dose and 30 (±5) minutes post-dose. The last two post-dose samples following 

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the first dose of IMP and the two steady-state dot-blot blood samples can be collected by subject 
or parent at home. 
7.2 
Drugs and Dosages 
Oral ifetroban is available as the sodium salt of the free acid and is for investigational use only. 
The drug is supplied as a capsule dosage form (size # 1, white opaque) for oral administration. 
Ifetroban capsules are formulated as a dry powder blend and filled into hard gelatin capsules.  The 
formulation consists of ifetroban, mannitol, microcrystalline cellulose, crospovidone, magnesium 
oxide, colloidal silicon dioxide, and magnesium stearate.  Capsules are filled into high density 
polyethylene bottles and sealed with screw-cap closures.  Capsules are only available at one 
strength of the sodium salt, i.e., 52.5 mg corresponding to a free-acid dose of 50 mg.  
Matching placebo capsules are formulated as a dry powder blend filled into capsules.  The 
formulation consists of microcrystalline cellulose, crospovidone, colloidal silicon dioxide, and 
magnesium stearate. Capsules are filled into high density polyethylene bottles and sealed with 
screw-cap closures. 
The bottles of oral ifetroban or placebo will contain the following information on the label:  
 
 
 
 
 
 
 
Additionally, each individual bottle will be labelled with a unique numeric code that identifies the 
contents to the unblinded sponsor representative. Subjects will be randomized to low-dose 
ifetroban, high-dose ifetroban or placebo. 
Low Dose:  < 35 kg: 50 mg, ≥ 35 kg: 100 mg/day 
High Dose: < 35 kg: 150 mg, ≥ 35 kg: 300 mg/day 
Table 7-1 Ifetroban Dose Levels & Sub-Groups 
DMD Sub-Group 
Low Dose 
High Dose 
Placebo 
Early Stage            
(LVEF > 45%) 
8 subjects 
8 subjects 
8 subjects 
PLACEBO OR IFETROBAN CAPSULES 50 MG 
Quantity: 75 Capsules 
Instruction: Take capsules by mouth as directed. 
Store at controlled room temperature, 20oC – 25oC (68oF – 77oF) 
Caution: New Drug-Limited by Federal law to investigational use 
Cumberland Pharmaceuticals Inc. 

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DMD Sub-Group 
Low Dose 
High Dose 
Placebo 
Advance Stage            
(current/historical 
LVEF 35-45%) 
8 subjects 
8 subjects 
8 subjects 
 
Should a subject experience an intolerable toxicity attributed to study drug the dose may be 
reduced by 50-mg decrements (one capsule) at a time at the investigator’s discretion. Any subject 
receiving 50 mg/day who experiences an intolerable toxicity attributed to study drug will be 
discontinued from the study. A subject may also have their dose held for up to two weeks to allow 
a severe adverse event to improve or resolve before considering resuming drug. IMP may resume 
at the starting dose or a reduced dose at the investigator’s discretion, once the toxicity has improved 
or resolved. Any subject with a serious toxicity that does not improve or resolve after a two week 
hold of IMP will be discontinued from the study. 
7.3 
Selection of Study Population 
Study eligibility will be determined by the Investigator based on the inclusion and exclusion 
criteria below. 
7.3.1 
Inclusion Criteria 
Individuals who meet all of the following criteria are eligible for enrollment as study subjects: 
1. Males 7 years of age and older with the diagnosis of DMD, defined as phenotype consistent 
with DMD and either positive genotype, first degree relative with positive genotype, or 
confirmatory muscle biopsy.  
2. Stable dose of oral corticosteroids for at least 8 weeks or has not received corticosteroids 
for at least 30 days. 
3. Stable cardiac function defined as change in LVEF of < 15% and no heart failure 
admission over the last 12 months; LVEF 35% or greater by cine CMR or 
echocardiography; myocardial damage in one or more left ventricular segments evident 
by late gadolinium enhancement allowed; concurrent angiotensin-converting enzyme 
inhibitors (ACEI), beta-blocker (BB) or angiotensin receptor blocker (ARB) therapy 
allowed (selection of which dictated by clinical care) if started three months or greater 
from first dose of IMP without change in dose. Aldosterone receptor antagonists (e.g. 
spironolactone or eplerenone) allowed if started 12 months or greater from first dose of 
IMP. No changes throughout the study allowed except in the event of a decline in left 

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ventricular ejection fraction (LVEF) >5% following the baseline CMR as measured by a 
subsequent CMR at the same center. Should this occur, changes in cardiac medications are 
allowed on study, and the patient may remain on IMP. 
a. Late-stage cohort: Subjects are eligible for the late-stage cohort if the subject has: 
i. LVEF 35%-45% by cine cardiac magnetic resonance imaging (MRI) or 
echocardiography or  
ii. historically documented LVEF 35%-45% by cine cardiac magnetic resonance 
imaging (MRI) or echocardiography and if their baseline MRI is less than 50%. 
 
4. Subjects aged 18 years and older, informed consent obtained directly. For subjects ages 7–
17 years old (yo), both assent from the subject and permission from a parent or guardian.  
5. AAV-based gene therapy permitted if ≥ 2 years from AAV administration and subject has 
documented cardiac decline defined as >5% decline in LVEF over a 2-year period 
following AAV administration using consecutive CMRs or echocardiography performed 
at the same center (must still meet inclusion criterion #3). 
7.3.2 
Exclusion Criteria 
Individuals who meet any of these criteria are not eligible for enrollment as study subjects: 
1. Clinically significant illness other than DMD 
2. Clinically significant laboratory abnormality not associated with DMD 
3. Major surgery within six weeks prior to the first dose of study drug, or planned surgery 
during this study which would interfere with the ability to perform study procedures 
4. Require antiarrhythmic therapy and/or initiation of diuretic therapy for management of 
acute heart failure in the last 6 months  
5. A LVEF of < 35% by CMR and/or fractional shortening of < 15% based on (ECHO during 
screening 
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7. Allergy to gadolinium contrast or known renal insufficiency defined as abnormal cystatin 
C or creatinine above the upper limit of normal for age. The male serum reference ranges 
as follows: 
 Age 7-9 years - 0.2 - 0.6 mg/dL 
 Age 10-11 years - 0.3 - 0.7 mg/dL 
 Age 12-13 years - 0.4 - 0.8 mg/dL 
 Age 14-15 years - 0.5 - 0.9 mg/dL 
 Age 16 years or older - 0.8 - 1.3 mg/dL 
 
8. Non-MR compatible implants (e.g. neurostimulator, automatic implantable cardioverter-
defibrillator [AICD]) 
9. Subjects who participated in a therapeutic clinical trial within 30 days or five half-lives 
(whichever is longer) of study entry  
10. Any other condition that could interfere with the subject’s participation 
7.4 
Concomitant Medications  
A concomitant medication is any treatment received by the subject concomitantly to the IMP. All 
concomitant medication use will be tracked in the subject diary and recorded in the appropriate 
Case Report Form (CRF).   
The following concomitant medications are allowed:  
• ACEI, BB, and ARB therapies are allowed (selection of which dictated by clinical care) if 
started three months or greater from start of IMP treatment with no change in dose and no 
changes throughout the study, except in the event of a decline in left ventricular ejection 
fraction (LVEF) >5% following the baseline CMR as measured by a subsequent CMR at the 
same center. Should this occur, changes in cardiac medications are allowed on study, and the 
patient may remain on IMP. 
• Aldosterone receptor antagonists (e.g. spironolactone or eplerenone) allowed if started 12 
months or greater from first dose of IMP. No changes allowed throughout the study, except 
in the event of a decline in left ventricular ejection fraction (LVEF) >5% following the baseline 
CMR as measured by a subsequent CMR at the same center. Should this occur, changes in 
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• Oral corticosteroids are allowed if started at least 8 weeks or greater from start of IMP 
treatment with no change in dose and no changes throughout the study. If not currently on 
oral corticosteroid, the subject must not have received corticosteroids for at least 30 days 
from the start of IMP treatment.  
• Diuretics are allowed if there has not been an adjustment in dosing for 6 months (e.g. 
furosemide or equivalent) 
• FDA-approved antisense oligonucleotide (ASO) therapy for DMD: Eteplirsen, Golodirsen, 
Casimersen, and Viltolarsen 
• During the open-label extension period, use of givinostat, an FDA-approved therapy for 
DMD, is permitted. Changes to cardiac medications or the administration of additional 
cardiac medications, including angiotensin receptor/neprilysin inhibitors (ARNI) and 
sodium glucose cotransporter-2 (SGLT2) inhibitors, are permitted during the OLE. 
7.5 
Prohibited Medications and Procedures 
Before enrollment, a medication history will be collected for each subject to ensure that no 
prohibited medications will be taken during the study and no surgeries or prohibited procedures 
are planned. The following medications and procedures are prohibited throughout the study: 
• Major surgery within six weeks prior to the first dose of study drug, or planned surgery 
during this study which would interfere with the ability to perform study procedures 
• Use of warfarin or any other antiplatelet or anticoagulant medications in the last two weeks 
before starting treatment 
• Any investigational therapy for DMD 
• Any concomitant medication with a depressive or stimulating effect on respiration or the 
respiratory tract. 
7.6 
Dietary Requirements 
Multiple food effect studies have demonstrated that high fat, protein or carbohydrate meals all had 
a similar effect of decreasing the maximum serum concentration (Cmax) (average of 80-90%), 
prolonging the time of maximum plasma concentration (Tmax) (8-12 fold), and decreasing the area 
under the concentration time-curves from time zero to infinity (AUC0-∞) of ifetroban (average of 
25-35%) compared to the fasting state.  

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For this reason, IMP must be taken at least 30 minutes before a meal AND six hours after a 
meal.   
8 STUDY VISITS AND PROCEDURES 
8.1 
Overview – Schedule of Time and Events 
This clinical study will consist of a 12-week Screening Period (Week -12 to Week 0) and a 12-
month Treatment Period (Month 0 to Month 12). The study visits occur on the planned dates 
relative to the first dose of IMP as scheduled. The visit schedule should be adhered to within the 
visit window indicated. 
If a subject is prematurely discontinued from treatment, all assessments planned at the End of 
Treatment visit should be performed. Prior to all screening assessments, after discussion of 
participation in the study, the written consent form must be signed and dated. Although the 
screening assessments for this study are grouped under the heading of a single visit in this protocol, 
it is possible for them to be performed over more than one site visit if necessary, as long as the 
twelve-week screening period relative to the first dose of IMP is respected. Furthermore, the site 
may split the on-site study visits during the treatment period (Day 0, Month 6, Month 12 & Month 
24, if applicable) into two visits no more than 7 calendar days apart provided that each of the visit 
days remain within the protocol established window for the on-site study visits. Subjects that fail 
screening for exclusion criteria, for example concomitant medications, acute illness (upper 
respiratory tract infection), required drug-specific discontinuation periods or laboratory tests, may 
be rescreened for study eligibility. 
8.1.1 
Screening Period 
The Screening Period is defined as the 12-week period prior to Week 0 (IMP administration). 
Before the initiation of study-specific screening assessments, the subject, and their parent or 
guardian if the subject is under 18 years of age, must be given a complete explanation of the 
purpose of the study and evaluations that will be made as part of the study. Subsequently, the 
subject, if 18 years and older, must sign and receive a copy of an Informed Consent Form that was 
approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC). For 
subjects ages 7–17 years, both assent from the subject and permission from a parent or guardian 
must be obtained. Once informed consent or assent and permission have been obtained, the 
eligibility of the subject to participate in this study will be determined by the Investigator on the 
basis of the inclusion and exclusion criteria in Section 7.3. Screening Period assessments will also 
be performed to determine eligibility. Only eligible subjects will be allowed to enroll and receive 

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IMP at the baseline visit (Week/Day 0). The following procedures will be performed to determine 
the subject’s eligibility for this study (Table 8-1) during the Screening Period (Week -12 to Week 
0): 
• Informed Consent for subjects 18 years and older; for subjects ages 7–17 years, both assent 
from the subject and permission from a parent or guardian.  
• Interview to collect subject medical history, including but not limited to, disease history, 
surgical history, dystrophin mutation, recently discontinued and concomitant medications 
(include all background therapy for DMD). 
• CMR or ECHO for eligibility or screening purposes; Baseline CMR must adhere to Study 
CMR protocol for efficacy endpoint or be repeated prior to starting IMP. 
The following procedures will be performed within two weeks of starting treatment (Week -2 to 
Week 0): 
• Obtain blood samples for screening clinical laboratory determinations: 
o Complete Blood Count with differential: must include hemoglobin, hematocrit, 
platelet count, total white blood cell count with five-part differential count, and total 
red blood cell count.  
o Comprehensive Metabolic Panel: must include serum creatinine, blood urea 
nitrogen, glucose, total protein, albumin, total bilirubin, alanine aminotransferase, 
aspartate aminotransferase, alkaline phosphatase, electrolytes (sodium, potassium, 
chloride), calcium, bicarbonate, and creatine phosphokinase. 
o Coagulation Factors: prothrombin time reported as the international normalized 
ratio (INR) value (prothrombin time- PT-INR), partial thromboplastin time (PTT or 
aPTT). 
o Cystatin C 
• Review entry criteria to assess eligibility.  
• Perform ECG, physical examination including vital signs (blood pressure, heart rate, 
respiration rate, body temperature, weight [kg], height [cm]) and record demographic data. 
• Schedule appointment for next visit. 

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8.1.2 
Treatment Period 
Week 0 Start of Treatment Visit  
Once the subject is confirmed eligible, the subject will have his Week 0 assessments completed. 
This can be done at the same screening visit or a separate visit within two weeks of the screening 
visit. 
• Interval history, record baseline signs and symptoms, record all medication use with start 
date and dose and check for prohibited medications. 
• Baseline PFT including PEF, FVC, FEV1, MIP, and MEP  
• Baseline PedsQL, GI module & NMM 
• Baseline QMT & Actigraphy 
• Reconfirm eligibility based on review of Inclusion/Exclusion criteria 
Note: Clinical laboratory testing at Week 0 Visit is limited to biomarkers in serum and plasma if 
screening labs were performed within two weeks of starting IMP treatment. Screening labs 
must be repeated if performed over 2 weeks from the baseline visit 
• Collect urine and blood samples for eicosanoid metabolites and other biomarkers.  
• Collect PK pre-dose dot-blot blood sample 
• Pre-IMP Dietary Assessment (confirm last meal was over six hours ago) 
• Dispense and administer IMP 
• Collect post-dose dot-blot PK blood samples: 30, 60 (±5) minutes; 4, 8 and 24 hours (all ± 
30 minutes) post first dose (24-hour PK sample is prior to 2nd dose; 8 and 24 hour samples 
can be collected at home) 
• Collect adverse event(s) (AE)  
• Schedule appointment for next visit 
Week 1 (May be collected at home by subject) 
• Collect PK pre-dose dot-blot blood sample 

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• Administer IMP in a fasted state (last meal was over six hours ago and next meal after 
administration is at least 30 minutes later) 
• Collect PK post-dose dot-blot blood sample at 30 (±5) minutes post-dose 
Week 1, Month 1, 3, 5, 7, 9 & 11 Phone Calls 
• Inquire about AEs/Serious Adverse Events (SAEs) and IMP tolerability 
• Record all medication use with start date and dose; check for prohibited medications 
• Confirm compliance (subject diary & pill counting) & dietary requirement 
• Remind subject to complete and return at-home PedsQL, GI module & NMM (Month 3 
& 9 only) 
Should the subject report a new or worsening symptom, additional safety phone calls and/or safety 
visits may be scheduled at the investigator’s discretion and safety labs performed. Any new or 
worsening abnormal lab should be followed and repeated until back to baseline or resolved. 
Month 3 At-home Quality-of-Life surveys 
• Complete and return Month 3 at-home PedsQL, GI module & NMM 
Month 6 Treatment Visit  
After six months of treatment, subjects will return to the site for Month 6 Treatment Visit. 
• Record all medication use with start date and dose; check for prohibited medications. 
• Inquire about AEs/Serious Adverse Events (SAEs) and IMP tolerability. 
• Confirm compliance (subject diary & pill counting) & dietary requirement. 
• Perform ECG, a physical exam with vital signs (blood pressure, heart rate, respiration rate, 
body temperature, weight). 
• Obtain blood samples for clinical laboratory tests: 
o Complete Blood Count with differential: must include hemoglobin, hematocrit, 
platelet count, total white blood cell count with five-part differential count, and total 
red blood cell count.  

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o Comprehensive Metabolic Panel: must include serum creatinine, blood urea 
nitrogen, glucose, total protein, albumin, total bilirubin, alanine aminotransferase, 
aspartate aminotransferase, alkaline phosphatase, electrolytes (sodium, potassium, 
chloride), calcium, bicarbonate, and creatine phosphokinase. 
o Coagulation Factors: prothrombin time reported as the international normalized 
ratio (INR) value (PT-INR), partial thromboplastin time (PTT or aPTT). 
• Collect urine and blood samples for eicosanoid metabolites and other biomarkers.  
• Dispense and administer IMP. 
• Optional Month 6 CMR (± 7 day window). If Month 6 CMR is declined, a mandatory 
ECHO should be performed. 
• Month 6 PFT including PEF, FVC, FEV1, MIP, and MEP  
• Month 6 PedsQL, GI module & NMM 
• Month 6 QMT & Actigraphy 
• Schedule appointment for next visit. 
Should the subject report a new or worsening symptom, additional safety phone calls and/or safety 
visits may be scheduled at the investigator’s discretion and safety labs performed. Any new or 
worsening abnormal lab should be followed and repeated until back to baseline or resolved. 
Month 9 At-home Quality-of-Life surveys 
• Complete and return Month 9 at-home PedsQL, GI module & NMM. 
Month 12 End of Treatment Visit  
After six additional months of treatment, subjects will return to the site for Month 12 End of 
Treatment Visit. 
• Record all medication use with start date and dose; check for prohibited medications. 
• Inquire about AEs/Serious Adverse Events (SAEs) and IMP tolerability. 
• Confirm compliance (subject diary & pill counting) & dietary requirement. 

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• Perform ECG, a physical exam with vital signs (blood pressure, heart rate, respiration rate, 
body temperature, weight). 
• Obtain blood samples for clinical laboratory tests: 
o Complete Blood Count with differential: must include hemoglobin, hematocrit, 
platelet count, total white blood cell count with five-part differential count, and total 
red blood cell count.  
o Comprehensive Metabolic Panel: must include serum creatinine, blood urea 
nitrogen, glucose, total protein, albumin, total bilirubin, alanine aminotransferase, 
aspartate aminotransferase, alkaline phosphatase, electrolytes (sodium, potassium, 
chloride), calcium, bicarbonate, and creatine phosphokinase. 
o Coagulation Factors: prothrombin time reported as the international normalized 
ratio (INR) value (PT-INR), partial thromboplastin time (PTT or aPTT). 
• Collect urine and blood samples for eicosanoid metabolites and other biomarkers.  
• Month 12 CMR (± 7 day window) 
• Month 12 PFT including PEF, FEV1, FVC, MIP and MEP 
• Month 12 PedsQL, GI module & NMM 
• Month 12 QMT & Actigraphy 
8.1.3 
Optional Open-Label Extension  
Patients who complete 12 months of treatment are eligible to participate in a repeatable open-label 
extension period of 12 months. Should a subject elect to participate in the open-label extension, 
the transition from IMP to the open-label extension should be continuous. Patients who elect to 
participate in the open-label extension will complete the following additional procedures. 
Month 15, 18 & 21 Phone Calls 
• Inquire about AEs/Serious Adverse Events (SAEs) and IMP tolerability 
• Record all medication use with start date and dose; check for prohibited medications 
• Confirm compliance (subject diary & pill counting) & dietary requirement 

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• Remind subject to complete and return at-home PedsQL, GI module & NMM (Month 18 
only) 
Should the subject report a new or worsening symptom, additional safety phone calls and/or safety 
visits may be scheduled at the investigator’s discretion and safety labs performed. Any new or 
worsening abnormal lab should be followed and repeated until back to baseline or resolved. 
Month 18 At-home Quality-of-Life surveys 
• Complete and return Month 18 at-home PedsQL, GI module & NMM 
Month 24 Treatment Visit  
After 12 additional months of treatment, subjects will return to the site for Month 24 Treatment 
Visit. 
• Record all medication use with start date and dose; check for prohibited medications. 
• Inquire about AEs/Serious Adverse Events (SAEs) and IMP tolerability. 
• Confirm compliance (subject diary & pill counting) & dietary requirement. 
• Perform ECG, a physical exam with vital signs (blood pressure, heart rate, respiration rate, 
body temperature, weight). 
• Obtain blood samples for clinical laboratory tests: 
o Complete Blood Count with differential: must include hemoglobin, hematocrit, 
platelet count, total white blood cell count with five-part differential count, and total 
red blood cell count.  
o Comprehensive Metabolic Panel: must include serum creatinine, blood urea 
nitrogen, glucose, total protein, albumin, total bilirubin, alanine aminotransferase, 
aspartate aminotransferase, alkaline phosphatase, electrolytes (sodium, potassium, 
chloride), calcium, bicarbonate, and creatine phosphokinase. 
o Coagulation Factors: prothrombin time reported as the international normalized 
ratio (INR) value (PT-INR), partial thromboplastin time (PTT or aPTT). 
• Collect urine and blood samples for eicosanoid metabolites and other biomarkers.  
• Month 24 CMR (± 7 day window) 

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• Month 24 PFT including PEF, FEV1, FVC, MIP and MEP 
• Month 24 PedsQL, GI module & NMM 
• Month 24 QMT & Actigraphy 
Month 27, 30 & 33 Phone Calls 
• Inquire about AEs/Serious Adverse Events (SAEs) and IMP tolerability 
• Record all medication use with start date and dose; check for prohibited medications 
• Confirm compliance (subject diary & pill counting) & dietary requirement 
Should the subject report a new or worsening symptom, additional safety phone calls and/or safety 
visits may be scheduled at the investigator’s discretion and safety labs performed. Any new or 
worsening abnormal lab should be followed and repeated until back to baseline or resolved. 
Month 36 Treatment Visit  
After 24 months of open label treatment, subjects will return to the site for Month 36 Treatment 
Visit. 
• Record all medication use with start date and dose; check for prohibited medications. 
• Inquire about AEs/Serious Adverse Events (SAEs) and IMP tolerability. 
• Confirm compliance (subject diary & pill counting) & dietary requirement. 
• Perform ECG, a physical exam with vital signs (blood pressure, heart rate, respiration rate, 
body temperature, weight). 
• Obtain blood samples for clinical laboratory tests: 
o Complete Blood Count with differential: must include hemoglobin, hematocrit, 
platelet count, total white blood cell count with five-part differential count, and total 
red blood cell count.  
o Comprehensive Metabolic Panel: must include serum creatinine, blood urea 
nitrogen, glucose, total protein, albumin, total bilirubin, alanine aminotransferase, 
aspartate aminotransferase, alkaline phosphatase, electrolytes (sodium, potassium, 
chloride), calcium, bicarbonate, and creatine phosphokinase. 

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o Coagulation Factors: prothrombin time reported as the international normalized 
ratio (INR) value (PT-INR), partial thromboplastin time (PTT or aPTT). 
• Collect urine and blood samples for eicosanoid metabolites and other biomarkers.  
• Month 36 CMR (± 7 day window) 
• Month 36 PFT including PEF, FEV1, FVC, MIP and MEP 
If patients opt into additional 12-month open-label extension periods beyond Month 36, each 12-
month period will follow the same schedule outlined for the second 12-month open-label extension 
period above (Month 24 to Month 36).

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Table 8-1 
Schedule of Treatment & Events 
  
Screening Period 
Treatment Period 
Opt Ext 
Opt Ext 2g 
  
Visit(s) 
Visitf 
Phone 
Call/At-
home 
Phone Call 
At-home 
Visitf 
Visitf 
Phone 
Call/At-
home 
Visitf 
Phone 
Call/At-
home 
Visitf 
  
Week -12 
to Week 0 
Week -2 
to Week 
0 
Day 0 
Week 1    
(± 2 days) 
(At home) 
Month 1    
(± 2 days) 
Month 
3,5,7,9,11    
(± 7 days) 
Month 3 
& 9       
(At home) 
Month 6   
(± 7 days) 
Month 
12       
(± 7 
days) 
Month 
15, 18 & 
21       
(± 7 
days) 
Month 
24       
(± 7 
days) 
Month 
27, 30 & 
33       
(± 7 
days) 
Month 
36       
(± 7 
days) 
Informed Consent/Assent 
X 
  
  
  
  
  
  
  
  
  
 
 
Medical/Surgical History, 
Demography 
X 
  
  
  
  
  
  
  
  
  
 
 
Screening CMR or ECHO 
Xa 
  
  
  
  
  
  
  
  
  
 
 
Cystatin C 
  
X 
  
  
  
  
  
  
  
  
 
 
Research CMR 
  
Xa 
  
  
  
Xd 
X 
  
X 
  
X 
Physical Exam, Vital Signs 
  
X 
Xb 
  
  
  
X 
X 
  
X 
  
X 
Pulmonary Function Test 
  
  
X 
  
  
  
X 
X 
  
X 
  
X 
ECG, QMT & Actigraphy 
  
  
X 
  
  
  
X 
X 
  
X 
  
Xh 
PROs: PedsQL, GI & NMM 
  
  
X 
  
  
X 
X 
X 
Xe 
X 
 
 
CBC, CMP & Coagulation  
  
X 
Xb 
  
  
  
X 
X 
  
X 
  
X 
PK Blood Sampling 
  
  
Xc 
Xc 
  
  
  
  
  
  
  
  
Urine & blood for 
biomarkers 
  
  
X 
  
  
  
X 
X 
  
X 
  
X 
Review subject diary 
  
  
X 
  
  
  
X 
X 
  
X 
  
X 
Dispense IMP 
  
  
X 
  
  
  
X 
  
  
  
  
  
IMP Daily Dosing 
  
  
I--------------------------Continual Once Daily Dosing --------------------------------------------------------------------I 
Record Concomitant 
Medications 
  
I-----------------------------------Continual------------------------------------------------------------------------------------I 
AE/SAE Recording (if any) 
  
I-----------------------------------Continual------------------------------------------------------------------------------------I 
a –If screening CMR follows study-specific CMR protocol and was performed within 12 weeks of Baseline visit, Baseline CMR does not need to be repeated. 
b – Screening Physical Exam, Complete blood count (CBC), Comprehensive metabolic panel (CMP) & Coagulation within 2 weeks of Baseline Visit need not be repeated.  
c – PK blood sampling on Day 0: pre-dose, 30, 60 (±5) minutes; and 4, 8 and 24 hours (all ± 30 minutes) post dose. Day 7 (by subject at home): pre-dose and 30, (±5) minutes post-dose 
d – Month 6 CMR is optional. If the Month 6 CMR is declined, a mandatory ECHO should be performed. 
e – Quality of life questionnaires are to be completed at home at Month 18 only. Safety phone calls are completed at Months 15, 18 and 21. 
f - The site may split on-site study visits on Day 0, Month 6, Month 12, Month 24, and Month36 into two visits no more than 7 calendar days apart provided that each of the visit days remain within the 
protocol established window for the on-site Study Visits. 
g - If patients opt into additional 12-month open-label extension periods, each 12-month period will follow the same schedule outlined for the second 12-month open-label extension period above. 
h- ECG only; QMT and actigraphy not collected following Month 24 

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9 SUBJECT DISCONTINUATION AND STUDY OR SITE 
TERMINATION 
9.1 
Subject Discontinuation 
Subjects will be encouraged to complete the study; however, they may voluntarily withdraw at any 
time.  The Investigator will provide a report in the CRF describing the reason for discontinuation.  
If a subject withdraws before completion, every effort should be made to complete the assessments 
scheduled during the final scheduled assessment.     
A subject may be terminated early from the study for the following reasons: 
• The subject elects to withdraw consent from all future study activities, including follow-
up. 
• The subject is “lost to follow-up” (i.e., no further follow-up is possible because attempts to 
reestablish contact with the participant have failed). 
• The subject dies. 
• The subject develops a medical condition or is started on new medication(s) prohibited by 
the study or not previously mentioned in the list of prohibited medications that, in the 
opinion of the investigator, may pose additional risks from participation in the study, may 
interfere with the subject’s ability to comply with study requirements or that may impact 
the quality of the data obtained from the study. 
Subjects who are prematurely terminated from the study will be followed to monitor safety for a 
minimum of 30 days or until resolution of the disqualifying event, whichever is longer, or until the 
Independent Safety Monitor, the CPI Director of Medical Affairs and the Principal Investigator 
determine that the follow-up is complete. 
9.2 
Study or Site Termination 
If the Sponsor, Investigator, Independent Safety Monitor, Study Monitor, or appropriate regulatory 
officials discover conditions arising during the study that indicate that the study should be halted 
or that the study center should be terminated, this action may be taken after appropriate 
consultation among the Sponsor, Investigator, Independent Safety Monitor, and Study Monitor.   
Conditions that may warrant termination of the study include, but are not limited to, the following: 

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• The discovery of an unexpected, serious, or unacceptable risk to the subjects enrolled in 
the study 
• A decision on the part of the Sponsor to suspend or discontinue testing, evaluation, or 
development of the product 
• A study conducted at a single study site or a single study site in a multicenter study may 
also warrant termination under the following conditions: 
o Failure of the Investigator to enroll subjects into the study at an acceptable rate 
o Failure of the Investigator to comply with pertinent regulations of appropriate 
regulatory authorities 
o Submission of knowingly false information from the research facility to the 
Sponsor, Study Monitor, or appropriate regulatory authority 
o Insufficient adherence to protocol requirements 
Study termination and follow-up will be performed in compliance with the conditions set forth in 
the International Conference on Harmonization (ICH) sixth efficacy publication (E6) on Good 
Clinical Practice, section 4.12, ICH E6 4.13, ICH E6 5.20, and ICH E6 5.21. 
10 ADVERSE EVENTS 
Adverse events will be captured in the CRF for this study.   
10.1 
Definitions 
10.1.1 
 Adverse Event Definitions 
Adverse events are defined according to ICH Harmonized Tripartite Guideline E2A and 21 CFR 
312.32. 
Adverse event (AE) – is any untoward medical occurrence in a subject or clinical trial subject 
administered a trial product and which does not necessarily have a causal relationship with this 
treatment.  
An adverse event can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding, for example), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not considered related to the medicinal product. 

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The following is not considered or documented as an AE in study records: 
• Pre-planned procedure (documented as concomitant illness on the CRF at screening) unless 
the condition for which the procedure was planned has worsened from the first trial-related 
activity after the subject has signed the informed consent form. 
• Pre-existing conditions found as a result of screening procedures unless the condition 
worsens during treatment. 
• Events which are pre-defined as part of the efficacy analysis. However, if events are serious 
as defined below, events must be reported as such. 
Serious adverse event (SAE) – is any untoward medical occurrence or effect that at any dose: 
results in 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 refer to an event that hypothetically might have caused death 
if it was more severe); requires in-subject hospitalization or prolongation of existing 
hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly 
or birth defect; is judged medically important (this refers to an event that may not be immediately 
life-threatening or result in death or hospitalization, but may jeopardize the subject or may require 
intervention to prevent one of the other outcomes listed). 
10.1.2 Adverse Event Assessment Definitions 
Severity 
The maximum severity of an adverse event is assessed by the investigator using the following 
definitions:  
• Mild: Transient symptoms, no interference with the subject’s daily activities. 
• Moderate: Marked symptoms, moderate interference with the subject’s daily activities. 
• Severe: Considerable interference with the subject’s daily activities, unacceptable. 
Relationship 
The causal relationship between an adverse event and the trial product is assessed by the 
investigator using the following definitions: 
• Probable: Good reasons and sufficient documentation to assume a causal relationship. 
• Possible: A causal relationship is conceivable and cannot be dismissed  

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• Unlikely: The event is most likely related to an etiology other than the trial product. 
An adverse event is considered causally related to the use of the trial product when the relationship 
assessment is probable or possible. Events assessed as unlikely related to the use of trial product 
will generally be considered as having no relationship to treatment. 
Outcome 
The outcome of an adverse event is assessed by the investigator using the following definitions: 
• Recovered: Fully recovered, or by medical or surgical treatment the condition has returned 
to the level observed at the first trial-related activity. 
• Recovering: The condition is improving and the subject is expected to recover from the 
event. This term should only be used when the subject has completed the trial. 
• Recovered with sequelae: As a result of the AE the subject suffered persistent and 
significant disability/incapacity (e.g. became blind, deaf, paralyzed). Any AE recovered 
with sequelae should be classified as SAE.   
• Not recovered: The subject’s condition has not improved and the symptoms are unchanged 
• Fatal 
• Unknown: The subject’s condition is unknown. This term should only be used when no 
other definition is possible (e.g. the subject is lost to follow-up). 
10.2 
Collection, Recording and Reporting of Adverse Events 
For this study, all events meeting the definition of an adverse event must be collected and reported 
from the first trial-related activity after the subject signs the informed consent and until end of 
post-treatment period.  
The investigator should record the diagnosis, if available. If no diagnosis is available the 
investigator should record each sign and symptom as individual adverse events. 
The investigator must report initial information on all serious adverse events within 24 hours of 
obtaining knowledge of the event. Furthermore, the investigator must complete the SAE forms 
within five days of obtaining knowledge of the SAE. The monitor must be informed accordingly. 

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The investigator must inform the IRB in accordance with local requirements in force and the ICH 
guidelines for GCP and the Food and Drug Administration (FDA) Title 21 Code of Federal 
Regulations, Part 312.32. 
10.3 
Follow-up of Adverse Events 
All adverse events classified as non-serious adverse events that are both classified as severe and 
possibly or probably related to the investigational medicinal product must be followed until the 
subject has recovered and all queries have been resolved. 
For cases of chronic conditions, follow-up until “recovered” is not required. After the subject has 
completed the trial, these cases can be closed with the outcome “recovering” or “not recovered”. 
All other non-serious adverse events must be followed until the outcome of the event is 
“recovering” (for chronic conditions), “recovered” or until the last subject contact/visit/end of 
post-treatment follow-up period, whichever comes first, and until all queries related to the adverse 
event have been resolved. 
Follow-up of Serious Adverse Events 
All adverse events classified as serious should be followed until the outcome of the event is 
“recovered”, “recovered with sequelae”,  or “death” and until all queries have been resolved. For 
cases of chronic conditions and cancer, follow-up until “recovered”, “recovered with sequelae” or 
“death” is not required. After the subject has completed the trial, these cases can be closed with 
the outcome “recovering” or “not recovered”. 
11 STATISTICAL METHODS AND DATA ANALYSIS 
The following text provides a general description of the statistical methodology for the assessment 
of safety and tolerability of oral ifetroban in this randomized, double-blind, placebo-controlled, 
multiple dose study in subjects with DMD. Details of the statistical analyses will be provided in 
the Statistical Analysis Plan, which will be finalized prior to database lock.  All recorded data will 
be listed. 
11.1 
Sample Size Determination 
The sample size is based on the comparison of each dose level of ifetroban (Low Dose or High 
Dose) to placebo with respect to change from baseline in LVEF using CMR for each disease stage, 
early (LVEF > 45%) or advanced (current/historical LVEF 35-45%). Assuming observations from 
each treatment group have normal distributions with an effect size of 1.6 for the comparison of a 
dose of ifetroban to placebo, 8 subjects for each treatment group within disease stage will provide 

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power exceeding 85% for a t-test at two-sided level 0.05. Under these assumptions, 8 subjects for 
each treatment group within disease stage will provide power exceeding 80% for the Wilcoxon 
rank sum test at two-sided level 0.05. A total of 48 DMD subjects will be enrolled: 24 subjects with 
early stage DMD (LVEF > 45%) and 24 with advance stage DMD (current/historical LVEF 35-
45%). Assuming a dropout rate of 25%, 60 subjects will be recruited to meet the target sample size 
of 48 subjects.  
11.2 
Subject Populations for Analysis 
11.2.1 
 Safety Population 
All subjects who receive at least one dose of treatment will be included in the Safety Population.  
Treatment emergent period for Safety Population is defined as the time from the first 
administration of treatment to the end of the Treatment Period. 
11.2.2 
 Intent-to-Treat Population 
The Intent-To-Treat (ITT) Population will consist of all treated subjects with at least one post-
baseline assessment. 
11.2.3 
 Per Protocol Population 
The Per Protocol (PP) Population will consist of all subjects in the ITT population with no major 
protocol violations, including violation of inclusion or exclusion criteria or insufficient dosing 
where the latter includes missing more than 2 consecutive weeks of dosing for any reason or 
missing >20% of prescribed doses between consecutive visits. 
11.3 
Subgroup analysis 
To assess the consistency of treatment effects across the subgroup levels, and to examine baseline 
biomarkers for their potential value to predict treatment response, exploratory subgroup analyses 
will be conducted for safety, tolerability, pharmacokinetics and efficacy with respect to age group, 
race, DMD disease stage, baseline LVEF, muscle strain and other CMR parameters, baseline PFT, 
PedsQL, GI module & NMM values and selected biomarkers prior to the study. The details will 
be provided in the Statistical Analysis Plan. 
11.4 
Interim Analysis 
An early analysis will be performed when half the target enrollment has completed the six month 
visit and assessments. A decision to change the conduct of the study may be made based on this 
analysis. Key findings from the interim analysis will be summarized and distributed to limited 

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personnel. To maintain study integrity with respect to subsequent treatment visits, the team that 
will perform the early analysis and all related activities will be external and restricted from 
participating in data review or decisions following the early analysis but may participate in the 
analysis following final database lock. Statistical considerations related to the interim analysis will 
be provided in the Statistical Analysis Plan. 
11.5 
Historical Comparator 
Data collected from an FDA-funded DMD NHS will be used as a historical 
comparator/supplemental placebo group (Soslow 2023). The NHS utilized as a comparator is an 
ongoing, multi-year, multicenter study evaluating the natural progression of DMD. Eligibility is 
broad based on DMD diagnosis, and endpoints collected mirror endpoints collected for CPI-IFE-
007 except patient-reported outcomes (PedsQL). NHS visits are scheduled yearly, and 
demographic, baseline characteristics, medical history, and concomitant medication information is 
collected at each visit along with CMR, PFTs, QMT, and accelerometry. Patients from the NHS 
will be selected at a 2:1 ratio (NHS to placebo) using propensity score matching (PSM) based on 
baselined LVEF, age, and background DMD therapy with consideration for other relevant cardiac 
medications (ACEi, ARB, beta-blockers, ARNI, aldosterone receptor antagonists, diuretics, 
calcium channel blockers. Matched NHS patients will be added to the CPI-IFE-007 placebo group 
from the 12-month double-blind study to create a supplemental, representative placebo group of a 
larger size for Month 12 efficacy analyses. For the open label extension, a historical comparator 
group will be formed from NHS patients selected at a 2:1 ratio (NHS to open label high-dose 
ifetroban) using PSM as described above. The NHS comparator group for the open label extension 
will be compared with open-label high-dose ifetroban patients at Month 12, Month 24, and Month 
36.  
11.6 
Randomization 
Subjects will be randomly assigned to one of three treatment groups: low-dose ifetroban, high-
dose ifetroban, placebo, using a 1:1:1 randomization ratio. All subjects will be treated with IMP 
daily for at a minimum of six months and a maximum of 12 months.  

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11.7 
Methods for Handling Missing Data 
All missing data will be queried. Missing data which are not retrievable through queries will not 
be imputed. The only exception to this is one supportive analysis with missing LVEF at Month 12 
imputed by LVEF at Month 6; subjects missing LVEF at both Month 6 and Month 12 will be 
excluded from this supportive analysis. 
11.8 
Data Analysis Plan  
11.8.1 
Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be summarized by dose level and overall. 
11.8.2 
 Exposure and Compliance 
Exposure and compliance will be summarized for the Safety Population by dose level and overall. 
Comments recorded on the Study Drug Accountability CRF page will not be applied in the 
computation of compliance.  Exposure is the duration (days) of treatment, computed as: 
Exposure= Date of Final Dose- Date of Baseline Visit + 1.  
Treatment compliance will be calculated as: 
Compliance (%) = 100*(Total Number of Capsules Dispensed-Total Number of Capsules 
Returned)/ (Expected Usage), 
where Expected Usage= Exposure * number of capsules to have been taken daily (1 capsule for 
50 mg, 2 for 100 mg, 3 for 150 mg, or 6 for 300 mg). 
11.8.3 
Efficacy Analyses 
Between-treatment comparisons with respect to the change from baseline in LVEF and the change 
from baseline in myocardial strain at Month 6 and Month 12 will be performed for the ITT and PP 
Populations using the Wilcoxon rank sum test. A supportive analysis with missing LVEF at Month 
12 imputed by LVEF at Month 6; subjects missing LVEF at both Month 6 and Month 12 will be 
excluded from this supportive analysis. In line with the current paradigm for the assessment of 
therapeutic efficacy in rare diseases and specifically DMD using established natural history data 
(Liu 2022, US FDA 2019, US FDA 2018), a comparison of the NHS-supplemented placebo group 
(2:1 NHS to placebo) will also be performed at Month 12 versus the high-dose ifetroban ITT and 
PP populations for CMR parameters. 
Summary statistics for other endpoints will be presented for both the ITT and PP Populations.  

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11.8.4 
 Safety Parameters 
All safety data will be summarized. AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) (Version 27.0 or later). All Treatment Emergent Adverse Events (TEAEs) 
will be summarized by treatment group. Counts and percents will be presented by dose level for 
each observed system organ class (SOC) and preferred term as defined in MedDRA.   
The preferred terms and SOCs will be summarized in the following set of tables: 
• 
All AEs; 
• 
All AEs by maximum level of severity; 
• 
All AEs by closest relationship to the study medication. 
The frequencies and percentages of AEs will be tabulated. Incidence, relation to study medication, 
and severity will be summarized. 
11.8.5 
 PK Analysis 
On the basis of plasma ifetroban and its acyl glucuronide metabolite concentration time data, the 
following PK parameters will be estimated by using a non-compartmental model: 
• AUC0-t, calculated by using the linear-log trapezoidal rule: linear trapezoidal rule up to 
time to maximum concentration, and then a log trapezoidal rule for the remainder of the 
curve, where t corresponds to the last measurable time point 
• AUC0-∞ = AUC0-t + Ct/λz, where Ct is the last measurable ifetroban concentration and λz 
is the terminal elimination rate constant calculated by using log linear regression of the 
terminal elimination phase of the plasma concentration versus time curve 
• Cmax of ifetroban estimated by inspection of the ifetroban concentration time curve 
• Tmax estimated by inspection of the ifetroban concentration time curve 
• Terminal T1/2 = ln(2)/λz 
11.8.6 
Long-Term Safety and Efficacy Analyses 
Subjects that complete the 12-month double-blind portion of the study will be eligible for an 
optional open label extension consisting of repeatable 12-month periods of treatment with high-
dose ifetroban.  
Safety will be monitored by continual adverse event reporting and changes in laboratory values as 
previously described. 

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For main efficacy endpoints (CMR parameters LVEF and myocardial strain), comparisons with 
respect to the change from Month 12 in LVEF and the change from Month 12 in myocardial strain 
at Months 24 and 36 will be performed for the ITT open label population using the Wilcoxon rank 
sum test. To assess treatment response the double-blind an open label studies, comparisons with 
respect to the change from baseline in LVEF and the change from baseline in myocardial strain at 
Months 24 and 36 will be performed for the ITT open label population using the Wilcoxon rank 
sum test. Subjects missing LVEF at either Month 12 or Month 24 will be excluded from this 
supportive analysis. 
12 STUDY MANAGEMENT AND DATA COLLECTION 
12.1 
Confidentiality 
All information regarding the nature of the proposed investigation provided by the Sponsor or 
Study Monitor to the Investigator (with the exception of information required by law or regulations 
to be disclosed to the IRB, the subject, or the appropriate regulatory authority) must be kept in 
confidence by the Investigator. 
The anonymity of participating subjects must be maintained. Subjects will be identified by an 
assigned subject number on CRFs and other study documents submitted to the Study Monitor. 
Documents that will not be submitted to the Study Monitor and that identify the subject (e.g., the 
signed informed consent document) must be maintained in strict confidence by the Investigator, 
except to the extent necessary to allow auditing by the appropriate regulatory authority, the Study 
Monitor, or Sponsor representatives. 
12.2 
Source Documents 
Source data are contained in source documents.  Examples of these original documents, and data 
records include: hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ 
diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies or transcriptions certified after verification as being accurate and complete, 
microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and 
records kept at the pharmacy, at the laboratories, and at medico-technical departments involved in 
the clinical trial. 
12.3 
Case Report Forms 
It is the responsibility of the Investigator to maintain adequate and accurate electronic CRFs 
(eCRF) designed by the Sponsor to record (according to Sponsor instructions) all observations and 

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other data pertinent to the clinical investigation in a timely manner. All CRFs should be completed 
in their entirety in a neat, legible manner to ensure accurate interpretation of data. 
Should a correction be made, the corrected information will be entered in the e-CRF overwriting 
the initial information. An audit trail allows for identifying the modification. 
Data are available within the system to the Sponsor as soon as they are entered in the e-CRF. 
 
The computerized handling of the data by the Sponsor when available in the eCRF may generate 
additional requests to which the Investigator is obliged to respond by confirming or modifying the 
data questioned. The requests with their responses will be managed through the eCRF.   
12.4 
Records Retention 
According to CFR21 312.62 (c) and ICH E6 4.9.5, all CRFs, as well as supporting documentation 
and administrative records, must be retained by the Investigator for a minimum of two years 
following notification that the appropriate regulatory authority has approved the product for the 
indication under study, if no application is to be filed or if the application is not approved for such 
indication, until two years after the investigation is discontinued and FDA is notified. It is the 
sponsor’s responsibility to inform the investigator as to when these documents no longer need to 
be retained. No study documents will be destroyed or moved to a new location without prior 
written approval from the Sponsor.  If the Investigator relocates, retires, or withdraws from the 
clinical study for any reason, all records required to be maintained for the study should be 
transferred to an agreed upon designee, such as the Study Monitor, another Investigator, or the 
institution where the study was conducted. 
13 STUDY MONITORING, AUDITING, AND INSPECTING 
13.1 
Study Monitoring Plan 
The progress of the study will be monitored by using the following methods: 
• Periodic on-site visit(s) 
• Safety Assessment Committee communications among the Clinical Monitor and Medical 
Monitor to conduct real-time unblinded reviews of the safety data at frequent intervals to 
take appropriate measures to ensure subjects are not placed at unreasonable risk of harm. 
• The relationship between exposure and safety and efficacy endpoints will be monitored 
and the need for dose adjustments for various extrinsic/intrinsic factors considered. 

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• Review of CRFs and clinical records 
14 ETHICAL CONSIDERATIONS 
This study will be conducted according to the standards of FDA, ICH, GCP Guidelines, IRB 
regulations, any applicable government regulations and procedures. This protocol and any 
amendments will be submitted to a properly constituted IRB for approval of the study conduct. 
14.1 
Informed Consent 
Written informed consent must be obtained from each subject (or the subject’s legal 
guardian/representative) before performing any Screening Period evaluations.  The signed 
informed consent document will be retained by the Investigator, and a copy will be given to the 
subject or subject’s legal guardian/representative.  The informed consent document, which is 
prepared by the Investigator, must have been reviewed and approved by the Sponsor and the 
Investigator’s IRB before the initiation of the study.  The document must contain the 20 elements 
of informed consent described in ICH E6 4.8 (Appendix 16.1).  Appendix 16.1 provides further 
details regarding the specific requirements for informed consent.  In addition, subjects ages 7–17 
years should provide written informed assent and parent or guardian must provide permission.  
14.2 
Protocol Compliance  
Substantive changes in the protocol include changes that affect the safety of subjects or changes 
that alter the scope of the investigation, the scientific quality of the study, the experimental design, 
dosages, assessment variable(s), the number of subjects treated, or the subject selection criteria.  
Such changes must be prepared as a protocol amendment by the Study Monitor and implemented 
only upon joint approval of the Sponsor, Investigator, and the Study Monitor.  A protocol 
amendment must receive IRB approval before implementation.  In parallel with the IRB approval 
process, the protocol amendment will be submitted to the appropriate regulatory authority as an 
amendment to the regulatory submission under which the study is being conducted.  If a protocol 
amendment requires changes in the informed consent document, the revised informed consent 
document prepared by the Investigator must be approved by the Sponsor, Study Monitor, and the 
IRB. 
Emergency departures from the protocol that eliminate an apparent immediate hazard to a 
particular subject and that are deemed crucial for the safety and well-being of that subject may be 
instituted for that subject only.  The Investigator or other attending physician also will contact the 
Medical Monitor as soon as possible in the case of such a departure.  These departures do not 
require pre-approval by the IRB; however, the IRB and Medical Monitor must be notified in 

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writing as soon as possible after the departure has been made.  In addition, the Investigator will 
document in the subject’s CRF the reasons for the protocol deviation and the ensuing events. 
14.3 
Study Files 
Documentation concerning Investigator data, IRB data, and clinical laboratory data is required 
before shipment of study drug to the study site (Appendix 16.2).  Copies of these documents as 
well as supplemental information, such as the Investigator’s Brochure and Responsibilities and 
Obligations of Investigators and Sponsors (Appendix 16.3.2), will be kept on-site in a special study 
file. 
This 
file 
also 
will 
contain 
drug 
accountability 
(receipt/dispensing) 
records, 
Sponsor/Investigator correspondence, IRB correspondence, changes to the protocol, information 
regarding monitoring activities, subject exclusion records, biological samples records, and CRFs.  
Investigator data, including FDA Form 1572 and statement of qualifications for each Investigator, 
are provided in Appendix 16.3.2. 
15 REFERENCES 
Acquaviva A, Vecchio D, Arezzini B, et al. Signaling pathways involved in isoprostane-mediated 
fibrogenic effects in rat hepatic stellate cells. Free Radic. Biol. Med. 2013;65:201-207. 
Audoly LP, Rocca B, Fabre JE, et al. Cardiovascular responses to the isoprostanes iPF(2α)-III and 
iPE(2)-III are mediated via the thromboxane A2 receptor in vivo. Circulation. 2000;101:2833–
2840. 
Comporti M, Signorini C, Arezzini B, et al. F2-isoprostanes are not just markers of oxidative stress. 
Free Radic. Biol. Med. 2008;44:247-256. 
Cracowski JL, Tremel F, Marpeau C, et al. Increased formation of f(2)-isoprostanes in patients 
with severe heart failure. Heart. 2000;84:438-441. 
D'Amario D, Amodeo A, Adorisio R, et al.  A current approach to heart failure in Duchenne 
muscular dystrophy Heart Published Online First: 01 July 2017. 
Francois H, Athirakul K, Mao L, et al. Role for thromboxane receptors in angiotensin-ii-induced 
hypertension. Hypertension. 2004;43:364-369. 
Francois H, Makhanova N, Ruiz P, et al. A role for the thromboxane receptor in l-name 
hypertension. Am. J. Physiol. Renal Physiol. 2008;295:F1096-1102. 

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Gelosa P, Sevin G, Pignieri A, et al. Terutroban, a thromboxane/prostaglandin endoperoxide 
receptor antagonist, prevents hypertensive vascular hypertrophy and fibrosis. Am. J. Physiol. Heart 
Circ. Physiol. 2011;300:H762-768. 
Hor KN, Wansapura J, Markham L, et al.  Circumferential strain analysis identifies strata of 
cardiomyopathy in Duchenne muscular dystrophy: a cardiac magnetic resonance tagging study. J 
Am Coll Cardiol. 2009;53:1204–1210. 
Huang JS, Ramamurthy SK, Lin X, et al. Cell signalling through thromboxane a2 receptors. Cell. 
Signal. 2004;16:521-533. 
Katugampola SD, Davenport AP. Thromboxane receptor density is increased in human 
cardiovascular disease with evidence for inhibition at therapeutic concentrations by the AT1 
receptor antagonist losartan. Br. J. Pharmacol. 2001;134:1385–1392. 
Kinsella BT, O'Mahony DJ, Fitzgerald GA. The human thromboxane a2 receptor alpha isoform 
(tp alpha) functionally couples to the g proteins gq and g11 in vivo and is activated by the 
isoprostane 8-epi prostaglandin f2 alpha. J. Pharmacol. Exp. Ther. 1997;281:957-964. 
Konagaya M, Takayanagi T. Regularity in the change of serum creatine kinase level in Duchenne 
muscular dystrophy. A study with long-term follow-up cases. Jpn J Med, 25 (1986), pp. 2-8. 
Lai Y, Zhao J, Yue Y, et al. Partial restoration of cardiac function with deltapdz nnos in aged mdx 
model of duchenne cardiomyopathy. Hum. Mol. Genet. 2014;23:3189-3199 
Liu J, Barrett JS, Leonardi ET, Lee L, et al. Natural History and Real-World Data in Rare Diseases: 
Applications, Limitations, and Future Perspectives. J Clin Pharmacol. 2022 Dec;62 Suppl 2(Suppl 
2):S38-S55. 
Quinlivan 
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dystrophy; 
http://www.orpha.net/consor/www/cgi-
bin/Disease_Search.php?lng=EN Last update September 2009. Accessed 14 Sept 2017. 
Rafael-Fortney JA, Chadwick JA, Raman SV. Duchenne muscular dystrophy mice and Men: Can 
understanding a genetic cardiomyopathy inform treatment of other myocardial diseases? Circ Res. 
2016;118(7):1059–61.  
Raman SV, Hor KN, Mazur W, et al. Eplerenone for early cardiomyopathy in Duchenne muscular 
dystrophy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2015; 14: 153–61. 

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Romfh, A, McNally EM. Cardiac assessment in Duchenne and Becker Muscular Dystrophies. 
Current Heart Failure Reports 2010: 7 (4): 212-28. 
Schumacher W, Heran C. Inhibition and Reversal of U-46,619-lnduced Myospastic Responses in 
Anesthetized Rats by SQ 34,451 and Other Thromboxane Antagonists. Internal Report 1990 Dec 
26. 
Schumacher W, Steinbacher T. Inhibition of Bronchospasm and Arterial Hypertension in Guinea 
Pigs by Oral and Intravenous Administration of SQ 34,451 and SQ 34,943. Internal Report 1990 
Dec 29. 
Soslow JH, Xu M, Slaughter JC, et al. Evaluation of Echocardiographic Measures of Left 
Ventricular Function in Patients with Duchenne Muscular Dystrophy: Assessment of 
Reproducibility and Comparison to Cardiac Magnetic Resonance Imaging. J Am Soc 
Echocardiogr. 2016;29(10):983–991. 
Soslow JH, Xu M, Slaughter JC, et al. Cardiovascular Measures of All-Cause Mortality in 
Duchenne 
Muscular 
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2023 
Aug;16(8):e010040. 
doi: 
10.1161/CIRCHEARTFAILURE.122.010040.  
Tandon A, Villa CR, Hor KN, et al. Myocardial Fibrosis Burden Predicts Left Ventricular Ejection 
Fraction and Is Associated With Age and Steroid Treatment Duration in Duchenne Muscular 
Dystrophy. Journal of the American Heart Association: Cardiovascular and Cerebrovascular 
Disease. 2015;4(4):e001338.  
U.S. Department of Health and Human Services Food and Drug Administration. Duchenne 
Muscular Dystrophy and Related Dystrophinopathies: Developing Drugs for Treatment Guidance 
for Industry: February 2018; https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/duchenne-muscular-dystrophy-and-related-dystrophinopathies-developing-drugs-
treatment-guidance (accessed 06 March 2025). 
U.S. Department of Health and Human Services Food and Drug Administration. Rare Diseases: 
Natural History Studies for Drug Development Guidance for Industry (Draft) March 2019: 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/rare-diseases-
natural-history-studies-drug-development (accessed 06 March 2025). 
Van Westering TLE, Betts CA, Wood MJA. Current Understanding of Molecular Pathology and 
Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy. Molecules 2015: 20: 8823-55. 

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Wacker MJ, Best SR, Kosloski LM, et al. Thromboxane a2-induced arrhythmias in the 
anesthetized rabbit. Am. J. Physiol. Heart Circ. Physiol. 2006;290:H1353-1361. 
Wacker MJ, Kosloski LM, Gilbert JR, et al.  Inhibition of thromboxane A2-induced arrhythmias 
and intracellular calcium changes in cardiac myocytes by blockade of the inositol trisphosphate 
pathway. J Pharmacol Exp Ther. 2009 Dec; 331(3):917-24. 
West JD, Voss BM, Pavliv L, et al.  Antagonism of the thromboxane-prostanoid receptor is 
cardioprotective against right ventricular pressure overload. Pulmonary Circulation. 
2016;6(2):211-223.  
West JD, Galindo CL, Kim K, et al. Antagonism of the Thromboxane-Prostanoid Receptor as a 
Potential Therapy for Cardiomyopathy of Muscular Dystrophy. J Am Heart Assoc. 2019 Nov 
5;8(21):e011902. 
Zhang Z, Vezza R, Plappert T, et al. COX-2-dependent cardiac failure in gh/ttg transgenic mice. 
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16 APPENDICES 
16.1 
Protection of Human Subjects  
Informed consent must be obtained from every subject before he enters a study.  It must be given 
freely and not under duress.  Consent must be documented by the subject or the subject’s legally 
authorized representative signing an IRB/IEC-approved consent form.  Subjects who do not speak 
English must be presented with a consent form written in a language that they understand.  A copy 
of the signed consent form must be given to the subject signing it.  The original must be kept in 
the Investigator’s files and made available to Sponsor and representatives of the appropriate 
regulatory authority upon request.  If, for any reason, subject risk is increased as the study 
progresses, a revised, IRB/IEC-approved consent form must be signed by the subject.  Before the 
study begins, a sample of the consent form must be provided to the Sponsor.  The appropriate 
regulatory authority may reject otherwise scientifically valid studies if proper informed consent 
has not been obtained from all subjects. 
16.1.1 
 Basic Elements Of Informed Consent 
Every consent form must include explanations of each of the following 20 elements: 
• That the trial involves research 
• The purpose of the trial 
• The trial treatment(s)  
• The trial procedures to be followed, including all invasive procedures 
• The subject’s responsibilities 
• Those aspects of the trial that are experimental 
• The reasonably foreseeable risks or inconveniences to the subject and, when applicable, to 
an embryo, fetus, or nursing infant 
• The reasonably expected benefits; and when there is no intended clinical benefit to the 
subject, the subject should be made aware of this 
• The alternative procedure(s) or course(s) of treatment that may be available to the subject, 
and their important potential benefits and risks 

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• The compensation and/or treatment available to the subject in the event of a trial-related 
injury 
• The anticipated prorated payment, if any, to the subject for participating in the trial 
• The anticipated expenses, if any, to the subject for participating in the trial 
• That the subject’s participation in the trial is voluntary and that the subject may refuse to 
participate or withdraw from the trial, at any time, without penalty or loss of benefits to 
which the subject is otherwise entitled 
• That the monitor(s), the auditor(s), the IRB/IEC, and the regulatory authority(ies) will be 
granted direct access to the subject’s original medical records for verification of clinical 
trial procedures and/or data, without violating the confidentiality of the subject, to the 
extent permitted by applicable laws and regulations and that, by signing a written informed 
consent form, the subject or the subject’s legally acceptable representative is authorizing 
such access 
• 
That the records identifying the subject will be kept confidential and, to the extent 
permitted by the applicable laws and/or regulations, will not be made publicly available; 
and if the results of the trial are published, the subject’s identity will remain confidential 
• 
That the subject or the subject’s legally acceptable representative will be informed in a 
timely manner if information becomes available that may be relevant to the subject’s 
willingness to continue participation in the trial 
• 
The person(s) to contact for further information regarding the trial and the rights of trial 
subjects, and whom to contact in the event of a trial-related injury 
• 
The foreseeable circumstances and/or reasons under which the subject’s participation in 
the trial may be terminated 
• 
The expected duration of the subject’s participation in the trial 
• 
The approximate number of subjects involved in the trial 
Nothing in these regulations is intended to limit the authority of a physician to provide emergency 
medical care to the extent the physician is permitted to do so under applicable federal, state, or 
local laws. 

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Informed consent allows the subject to fully understand his participation and serves to protect the 
Investigator and Sponsor from potential negligence claims.  A fully informed subject is the best 
protection against such claims. 
The informed consent requirements in these regulations are not intended to preempt any applicable 
federal, state, or local laws that require additional information to be disclosed in order that 
informed consent be legally effective.  Some states require further action on the Investigator’s part 
concerning subject consent. 
16.2 
Requisite Documents for Approval of Study Site 
Oral ifetroban sodium will be provided to the Investigators after they have submitted the following 
documents to the Study Monitor: 
• Signed protocol 
• Signed Statement of Investigator or FDA Form 1572 (if required by the regulatory agency) 
• Document indicating IRB/IEC approval of the final protocol, the informed consent and/or 
assent and recruitment advertisement documents (to include name, address, and 
chairperson of the IRB/IEC) 
• Blank copy of the IRB/IEC-approved informed consent document 
• Signed Investigator’s Agreement and Letter of Confidentiality 
• Clinical Laboratory Certification and normal ranges for tests that are performed in the 
laboratory for study assessments   
• Curricula vitae for the Investigator and Sub-Investigator(s) (i.e. individuals who, as part of 
an investigative team, will assist the investigator and make a direct and significant contribution 
to the data. In general, if an individual is directly involved in the performance of procedures 
required by the protocol, and the collection of data, that person should be listed on the 1572). 
• Financial disclosure Form FDA 3454 (any study FDA relies on to establish that the product 
is effective or any study in which a single investigator makes a significant contribution to 
the demonstration of safety). 
 

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16.3 
Responsibilities and Obligations of Investigators and Sponsors 
16.3.1 
Sponsor/Study Monitor 
The CPI Study Monitor will: 
Conduct a pre-investigation Site Selection Visit and/or Study Initiation Visit to: 
• Establish the acceptability of the facility and record the visit in a written report 
(i.e., memorandum or form). 
• Discuss with the Investigator the proposed clinical trial and supply draft CRFs, the 
Investigator’s Brochure, and the draft protocol for review and approval. 
• Discuss with the Investigator the regulatory requirements with respect to informed consent, 
IRB/IEC approval of the trial, the protocol, protocol amendments, and changes to the 
informed consent document. 
• Discuss with the Investigator the timing of interim and final reports to the Study Monitor 
and obligation to supply the Study Monitor with copies of all study-related documents 
(including IRB/IEC approval, IRB/IEC charter or equivalent, membership and 
qualifications, protocol amendments, informed consent documents, and consent changes), 
CRFs, CRF changes, and all pertinent correspondence to and from the IRB/IEC. 
Conduct periodic on-site visit(s) to: 
• Assure adherence to the protocol. 
• Review CRFs and hospital records for accuracy and completeness of information. 
• Examine pharmacy or other IMP storage and dispensing records for documentation of 
quantity and date of receipt of investigational drug, dispensation and accountability data 
for product administration to each subject, loss of materials, contamination, and unused 
supplies. 
• Record and report (summarize) observations on the progress of the trial and continued 
acceptability of the facilities, and prepare an on-site visit report. 
• Review Investigator files for required documents, (e.g., protocols; protocol amendments; 
Investigator’s Brochure; Study Procedures Manual; IRB/IEC approval of protocols, 

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amendments, and informed consent documents; IRB/IEC charter and membership; and 
communications to and from the IRB/IEC and the Study Monitor. 
16.3.2 
Investigator 
Institutional Review Board/Independent Ethics Committee 
The Investigator must assure the Study Monitor in writing that the Institutional Review 
Board/Independent Ethics Committee (IRB/IEC): 
• Meets FDA 21CFR 56 and/or ICH regulations as defined in ICH E 63: Institutional Review 
Board/Independent Ethics Committee (as applicable). 
• Has the authority delegated by the parent Institution and found in the IRB/IEC by-laws, 
operation guidelines, or charter to approve or disapprove clinical trials and protocols, 
including informed consent and other documents (e.g., protocol amendments and 
information to be supplied to subjects concerning informed consent). 
• Complies with proper personnel make-up of the Board. 
• Convenes meetings using acceptable rules of order for making decisions, recording such 
decisions, and implementing them. 
• Maintains files that contain (a) documentation of its decisions, such as are found in 
IRB/IEC minutes and correspondence, (b) written guidelines or by-laws governing 
IRB/IEC functions, (c) protocol, (d) protocol amendments, (e) approved informed consent 
document and information to be supplied to the subject, and (f) correspondence between 
the IRB/IEC and Investigator (e.g., consent changes, protocol amendments). 
Informed Consent of Human Subjects 
The Investigator must assure the Study Monitor in writing that the informed consent document for 
a subject: 
• Meets FDA 21CFR part 50 and/or ICH regulations as defined in ICH E6 4.8: Informed 
Consent of Trial Subjects (as applicable). 
• Has been approved by the IRB/IEC, including (when required) information to be given to 
the subject regarding the trial in which he is enrolled. 

IND 136895 
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Ifetroban Capsules 
 
CPI-IFE-007; Amendment 04a 
 
Page 61 
• Includes the basic elements and any additional elements of informed consent that are 
appropriate. 
• Has been signed by both the subject and the Investigator or designee, and a copy has been 
given to the subject. 
• May be provided to the subject in the "short form" informed consent document with written 
information as an alternative. 
Storage and Dispensing of Product Supplies 
The Investigator (or Pharmacist) must assure the Study Monitor in writing that: 
• Adequate and accurate written records show receipt and disposition of all product supplies, 
including dates, serial or lot numbers, quantities received, and each quantity dispensed, 
administered, or used, with identification of each subject. 
• Purpose and reasons are given in written records for product disposal (e.g., the amount 
contaminated, broken, or lost) and the quantity that was returned to the Sponsor. 
Case Report Forms 
The Investigator must assure the Study Monitor in writing that: 
• The completed CRF accurately reflects the hospital records for each subject. 
• The CRFs and hospital records will be accessible to the Clinical Monitor during on-site 
visits. 
Files and Records 
The Investigator must assure the quality, integrity, and content of his files, which will be subject 
to audit by the Study Monitor and the appropriate regulatory authority inspectors.  The files must 
contain, as minimum: 
• Correspondence to and from the IRB/IEC and to and from the Clinical Monitor. 
• Documents including the following: 
o IRB/IEC-approved protocols. 
o IRB/IEC-approved protocol amendments. 

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Ifetroban Capsules 
 
CPI-IFE-007; Amendment 04a 
 
Page 62 
o IRB/IEC-approved informed consent/assent documents and information to be supplied 
to the subject. 
o IRB/IEC-approved recruitment advertisement(s) 
o IRB/IEC charter, membership, and qualifications of each member. 
• Clinical supplies records including the following: 
o Receipt, date and quantity, and batch or lot number. 
o Disposition dates and quantity administered to each subject. 
o Inventory records. 
Documents and records must be retained by the Investigator for a period of two years following 
the date a marketing application is approved for the product for the indication for which it is being 
investigated, OR If no application is to be filed or if the application is not approved for such 
indication, until two years after the investigation is discontinued and the appropriate regulatory 
authority is notified.