Clinical trial NCT03470441
Conditions: Acute Myocardial Infarction STEMI
Sponsor: Faraday Pharmaceuticals, Inc.
Start date: 2017-10-27; Completion date: 2019-01-03
Enrollment: 120 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics (PK) of three dose levels of FDY-5301 compared to placebo in STEMI patients undergoing PCI.

Detailed description:
The purpose of this study is to evaluate the safety and effectiveness of an experimental drug called FDY-5301 as a possible treatment to reduce the size of the injury to the heart caused by the heart attack. An experimental drug is one that is being tested and is not approved by the United States Food and Drug Administration (FDA).

A heart attack occurs when a heart (coronary) artery supplying blood to the heart muscle becomes blocked and the heart muscle is injured. You will be having a cardiac catheterization procedure to clear the blockage in your coronary artery that caused your heart attack. This procedure works well but may not completely prevent some injury to the heart muscle which occurs when the blood supply is initially restored to the heart. This is known as "reperfusion injury".

FDY-5301 is a single intravenous injection. About 80 subjects are expected to participate in this study at about 20 research sites in the United States and Europe. Each subject's participation is expected to last about 6 months after receiving the study drug.

Subjects who meet all inclusion criteria will be randomly assigned to one of 4 study groups. Three groups will receive FDY-5301 (low, intermediate, or high dose) and 1 group will receive a placebo.The study drug (FDY-5301 or placebo) will be given through a vein (intravenously) during the catheterization procedure. This is a double-blind study so neither the patient nor study personnel will know whether the dose is active drug or placebo until the end of the study.

Arms: arm 1: Anticipated n=20 arm 2: Anticipated n=20 arm 3: Anticipated n=20 arm 4: Anticipated n=20
Interventions: intervention 1: FDY-5301 intervention 2: Placebo
Intervention descriptions: intervention 1: FDY-5301 will be administered once, intravenously, by a healthcare professional. Dosage will be administered on a body weight basis, according to treatment assignment and using the subject's body weight determined on the dose administration day. intervention 2: Placebo will be administered intravenously by a healthcare professional. Dosage will be administered on a body weight basis, according to treatment assignment and using the subject's body weight determined on the dose administration day.

Protocol documents:
Prot_002.pdf: 
Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 1 of 61 
FARADAY PHARMACEUTICALS, INC. 
FDY-5301-201-US 
 
Study Title: 
A Phase 2A, Randomized, Double-Blind, Placebo-
Controlled, Multi-Center Study of Intravenous FDY-5301 in 
Acute Myocardial Infarction 
Study Drug: 
FDY-5301 
Protocol Number: 
FDY-5301-201-US 
Drug Development 
Phase: 
2A 
Sponsor: 
Faraday Pharmaceuticals, Inc. 
1616 Eastlake Ave E, Suite 560 
Seattle, WA 98102 
(206) 492-5310 
Protocol Version/Date 
Version 2 / May 21, 2018 
 
 


Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 2 of 61 
Confidentiality Statement 
This document contains confidential information of Faraday Pharmaceuticals Inc. that must not be disclosed to anyone other than the 
recipient study staff and members of the study site. This information cannot be used for any purpose other than the evaluation or 
conduct of the clinical investigation without the prior written consent of Faraday Pharmaceuticals, Inc.  


Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 3 of 61 
INVESTIGATOR’S AGREEMENT 
I have read the attached protocol entitled “A Phase 2A, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of 
Intravenous FDY-5301 in Acute Myocardial Infarction” dated 09 May 2018 and agree to abide by all provisions set forth therein. 
I agree to comply with the International Conference on Harmonization Tripartite Guideline on Good Clinical Practice, the ethical 
principles stated in the latest version of the Declaration of Helsinki, and the applicable local and international regulations, whichever 
provide the greater protection of the individual. 
I agree to ensure that the confidential information contained in this document will not be used for any purpose other than the 
evaluation or conduct of the clinical investigation without the prior written consent of Faraday Pharmaceuticals, Inc. 
 
 
 
Signature 
 
 
 
 
 
Principal Investigator 
 
Date (DD Month YYYY) 
 
 
 
 
 
 


Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 4 of 61 
SPONSOR STATEMENT 
This study protocol was subject to critical review and has been approved by the following sponsor representative. 
 
 
 
Signature 
 
 
Simon Tulloch 
 
21 May 2018 
Chief Medical Officer  
 
Date (DD Month YYYY) 


Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 5 of 61 
1 
SYNOPSIS 
Name of Sponsor/Company: 
Faraday Pharmaceuticals, Inc. 
1616 Eastlake Ave E, Suite 560 
Seattle, WA 98102 
Name of Investigational Product: 
FDY-5301 
Name of Active Ingredient: 
Sodium Iodide (NaI) 
Title of Study:  
A Phase 2A, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of 
Intravenous FDY-5301 in Acute Myocardial Infarction 
Principal Investigator:  
TBD 
Sub-Investigator(s): 
TBD 
Estimated date first patient 
enrolled: 
3Q, 2017 
Estimated date last patient 
completed: 
2Q, 2018 
Phase of development:  
Phase 2A safety and efficacy study 
Purpose: 
To evaluate the safety, efficacy and pharmacokinetics (PK) of 3 dose levels of FDY-5301 
compared to placebo in patients presenting with an acute ST-segment elevation myocardial 
infarction (STEMI) undergoing percutaneous coronary intervention (PCI). 
Primary Outcome: 
The primary outcome for this study will be the combined number and incidence rate of 
several arrhythmias of interest for 14 days post study drug. These arrhythmias include 
ventricular fibrillation, sustained and non-sustained ventricular tachycardia and high degree 
AV block. Continuous cardiac monitoring will occur for 14 days post PCI by means of 


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FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 6 of 61 
wearable patch devices. 
Secondary Outcomes: 
Infarct size parameters will be assessed by cardiac magnetic resonance (CMR) at 72 +/-24 
hours post-study drug and 3 months post-study drug; the following will be compared between 
groups; infarct size as a proportion of ventricular volume (INF/VV), myocardial salvage 
index (MSI) and absolute myocardial infarction size (INF). 
 
The proportion of patients with ST-segment resolution at 4 hours post-study drug 
 
Serum levels of troponin calculated as AUC over 48 hours post treatment 
 
Persistent arrhythmias at 30 days and 3 months 
 
Measures of cardiac function by CMR including end-diastolic volume (EDV), end-systolic 
volume (ESV), fractional shortening (FS) and ejection fraction (EF) at discharge and 3 
months 
 
Biomarkers of cardiac injury, inflammation  and remodeling out to 3 months of follow up 
 
Cardiac related adverse events including the development of heart failure out to 3 months of 
follow up 
 
Incidence of all cause and cardiac mortality out to 6 months of follow up 
 
Additional Safety and tolerability: 
Physical examination including vital signs, clinical chemistry, hematology and thyroid 
function tests will be monitored. Adverse Events (AEs) and Serious Adverse Events (SAEs) 
will be recorded. 12 lead ECGs will be evaluated at intervals  and post baseline.  
Pharmacokinetics: 
Plasma iodide samples will be taken to estimate Cmax, AUC, Tmax and T1/2. 


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FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 7 of 61 
Methodology:  
This is a Phase 2A, randomized, double-blind, placebo-controlled, multi-center study that 
will evaluate safety, efficacy and PK of FDY-5301 in subjects with acute STEMI undergoing 
PCI. 
Up to 160 patients will be randomized to obtain a final sample size of 80 evaluable patients. 
By evaluable, we mean that a patient must have a complete dataset with regard to measures 
of arrhythmia data and infarct size. 
Subjects will receive either FDY-5301 or volume matched placebo after informed consent is 
obtained and a STEMI diagnosis has been made based on clinical and ECG findings, within 
an hour prior to myocardial reperfusion.  
All subjects will have an early CMR, 14 days of arrhythmia monitoring, and will be followed 
up for safety and efficacy for up to 6 months. Subjects will be monitored in hospital, and 
return for clinic visits at day 14, day 30 and 3 months post PCI. 
At the clinic visits, subjects will undergo evaluation to include measurement of laboratory 
safety parameters, adverse events, ECG. At the 3 month clinic visit, infarct size will also be 
assessed by CMR, and the presence of any persistent arrhythmias will be assessed by the 
investigator using an ECG rhythm strip. Follow up by phone to determine all cause and 
cardiac mortality status will occur at 6 months post-study drug. If the subject is unavailable 
then mortality status will be obtained from physician/investigator records.  
Number of patients: 
Up to 160 patients  
Diagnosis and main criteria for 
inclusion:  
1. 18-80 year old male subjects 
2. 18 to 80 year old female subjects who are not of child-bearing potential 
3. Accepted for Primary PCI with diagnosis of first STEMI, based on clinical and ECG 
criteria (ST-elevation at the J-point in two contiguous leads with the cut-off points: 
≥0.2 millivolt (mV) in men or ≥0.15 mV in women in leads V2-V3 and/or ≥0.1 mV in 
other leads) within 12 hours of symptom onset 
4. Written informed consent prior to study participation (either by the subject or a 


Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 8 of 61 
legally authorized representative of the subject) 
Exclusion Criteria: 
1. Previous myocardial infarction 
2. Left bundle branch block (LBBB) 
3. Previous coronary artery bypass graft surgery (CABG) 
4. Major hemodynamic instability or uncontrolled ventricular arrhythmias 
5. Known contraindication to CMR (e.g. pacemaker) 
6. Patients with known thyroid disease, or known allergy to iodide 
7. Subjects with past or current renal impairment requiring dialysis 
8. Pregnant or females of childbearing potential 
9. Body weight > 120 kg or Body Mass Index (BMI) > 35 kg/m2 
10. Use of investigational drugs or devices within 30 days prior to enrollment into the 
study 
11. Life expectancy of less than 1 year due to non-cardiac pathology 
12. Any clinically significant abnormality identified at the time of screening that in the 
judgment of the Investigator or any sub-Investigator would preclude safe completion 
of the study 
 
Investigational product, dosage and 
mode of administration:  
FDY-5301 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg or placebo will be administered intravenously 
(IV) by bolus injection between an hour and 5 minutes prior to coronary artery reperfusion. 
Duration of treatment: 
  
Treatment is a single IV bolus administration of study drug. Each subject will be involved up 
to 6 months from screening until study exit. 
Reference therapy, dosage and 
mode of administration:  
Placebo (normal saline for injection). Placebo will be indistinguishable from FDY-5301. 
Statistical methods: 
The primary outcome for this study will be the combined number and incidence rate of 


Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 9 of 61 
several arrhythmias of interest that occur in each group over a 14 day period post-study drug. 
These arrhythmias including ventricular fibrillation, sustained ventricular tachycardia (≥125 
BPM, ≥ 30 seconds), non-sustained ventricular tachycardia (≥ 125 BPM, ≥ 16 beats, < 30 
seconds) and high degree AV block ( 2nd or 3rd degree, ≥ 8 beats) were chosen because they 
are significant prognostic indicators of depressed left ventricular ejection fraction and cardiac 
death [1]. The combined number of arrhythmic events in each group will be calculated along 
with the arrhythmia incidence rate defined as the percentage of patients in each group 
experiencing at least one of the defined arrhythmias of interest.  
An exploratory sub-analysis will be conducted to determine the number and incidence rate of 
each separate arrhythmia type per dose group.  
Little data exists on the incidence of arrhythmias that occur over an extended period of time 
following AMI and monitoring strategies for this type of assessment have not been optimized 
in a clinical trial setting. The primary goal of our study is to characterize the occurrence of 
arrhythmias in this patient population for 14 days post-AMI and to determine the feasibility 
of using ambulatory patch ECG monitors to capture this data.  These data should be regarded 
as exploratory with the objective of identifying a meaningful clinical end point that can be 
easily measured in future, pivotal studies that are adequately powered to detect differences 
across treatment groups.     
As this is the first clinical study in patients, safety is the primary focus. For this reason, the 
goal is to enroll a limited number of patients to FDY-5301 while still powering the study to 
detect significant differences in efficacy measures across groups. Estimating a drop-out rate 
of 50%, we will need to enroll up to 160 patients in order to obtain a final total sample size of 
80 patients. A final sample size of 80 patients will provide 80% power to detect a 37% 
reduction in INF/VV assuming an SD of 10%, a 24% increase in MSI assuming an SD of 
20% and a 39% reduction in Troponin AUC with an SD of 60%. Equal variance was 
assumed among groups with an unbalanced allocation of patients to placebo (n=20) and 
combined FDY-5301 treatment groups (n=60). 


Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 10 of 61 
Exploratory efficacy outcomes will include: 
Between group comparisons of infarct size as a proportion of ventricular volume (INF/VV), 
the myocardial salvage index (MSI), and absolute MI size (INF) at 72 +/- 24 hours and 3 
months post PCI as measured by CMR will be performed. 
 
 
The proportion of patients with ST-segment resolution at 4 hours post study drug. 
Serum levels of troponin calculated as AUC 0-48 hours post study drug.  
Cardiac-related adverse events including the development of heart failure out to 3 months of 
follow up 
The incidence of all cause and cardiac mortality out to 6 months post PCI. 
In addition to the measurement of safety and efficacy parameters in this study, serum 
biomarker levels of cardiac injury, inflammation and remodeling will also be assessed.  
After the 14 day follow up visit to the clinic, analysis of all subjects’ data will be collected 
and analyzed for safety (arrhythmias) and early efficacy outcomes. 
After the 3 month follow up visit, analysis of efficacy outcomes including final MSI, 
INF/VV, INF parameters and cardiac function including EDV, ESV, FS and EF will be 
analyzed. All remaining assessments will be analyzed at the conclusion of the study.  
For PK analysis, Cmax, AUC, Tmax and T1/2 will be calculated for each dose based on plasma 
iodide levels. 


Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 11 of 61 
Document History 
Protocol Number: 
FDY-5301-201 
 
Original Protocol 
Date: 
August 30, 2017 
 
Amendment Number 
Amendment Date 
Explanation of Changes 
 
 
 
 
 
 
 
 
 
 


Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 12 of 61 
Table 1: Emergency Contact Information 
Clinical Research Organization (CRO) 
Role in Study 
Name 
Address and Telephone Number 
Study Project Leader 
TBD 
 
Medical Monitor 
TBD 
 
 
 
Sponsor Representative 
Role in Study 
Name 
Address and Telephone Number 
Medical Monitor 
TBD 
 


Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 13 of 61 
TABLE OF CONTENTS 
1 
SYNOPSIS .................................................................................................................... 5 
2 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ........................... 17 
3 
INTRODUCTION...................................................................................................... 20 
3.1 
Disease ......................................................................................................................... 20 
3.2 
FDY-5301 Background ................................................................................................ 20 
3.3 
Rationale ...................................................................................................................... 21 
4 
TRIAL OBJECTIVES AND PURPOSE ................................................................. 22 
4.1 
Primary Outcome ......................................................................................................... 22 
4.2 
Secondary Outcomes ................................................................................................... 22 
5 
INVESTIGATIONAL PLAN ................................................................................... 24 
5.1 
Overall Study Design and Plan: Description ............................................................... 24 
5.2 
Number of Centers/Subjects ........................................................................................ 24 
5.3 
Estimated Study Duration ............................................................................................ 25 
5.4 
Assignment to Study .................................................................................................... 25 
5.5 
Schedule of Assessments ............................................................................................. 25 
5.5.1 
Screening (Day 1 – Prior to PCI) ................................................................................. 25 
5.5.2 
Treatment Day 1 – in Cardiac Catheterization Lab and Recovery .............................. 26 
5.5.3 
Day 2 (24 hours +/- 2 hours post-study drug) .............................................................. 27 
5.5.4 
Day 3 (48 hours +/- 2 hours post-study drug) .............................................................. 27 
5.5.5 
First CMR (72 hours +/- 24 hours post-study drug) .................................................... 27 
5.5.6 
Follow-up 14 days (+/- 2 days post drug) .................................................................... 28 
5.5.7 
Follow-up 30 days (+/- 1 week post drug) ................................................................... 28 
5.5.8 
Follow-up 3 months (+/- 2 weeks post drug) ............................................................... 28 
5.5.9 
Follow-up 6 months or early termination (+/- 4 weeks post drug) .............................. 29 
6 
SELECTION AND WITHDRAWAL OF SUBJECTS .......................................... 32 
6.1 
Subject Inclusion Criteria ............................................................................................ 32 
6.2 
Subject Exclusion Criteria ........................................................................................... 32 


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FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 14 of 61 
6.3 
Subject Withdrawal Criteria ........................................................................................ 32 
6.4 
Early Termination Visit ............................................................................................... 33 
7 
STUDY TREATMENTS ........................................................................................... 34 
7.1 
Description of Study Drug ........................................................................................... 34 
7.2 
Concomitant Medications ............................................................................................ 34 
7.3 
Randomization and Blinding ....................................................................................... 34 
8 
STUDY DRUG MATERIALS AND MANAGEMENT ......................................... 35 
8.1 
Study Drug ................................................................................................................... 35 
8.2 
Study Drug Packaging and Labeling ........................................................................... 35 
8.3 
Study Drug Storage ...................................................................................................... 35 
8.4 
Study Drug Preparation................................................................................................ 35 
8.5 
Administration ............................................................................................................. 36 
8.6 
Study Drug Accountability .......................................................................................... 36 
8.7 
Study Drug Handling and Disposal ............................................................................. 36 
9 
REPLACEMENT OF SUBJECTS ........................................................................... 38 
10 
CMR PROTOCOL .................................................................................................... 39 
11 
STUDY OUTCOMES ................................................................................................ 40 
12 
ASSESSMENT OF PHARMACOKINETICS, TROPONIN AND LABORATORY SAFETY MEASURES 
42 
12.1 
Pharmacokinetics: Blood Iodide Levels ...................................................................... 42 
12.1.1 
Pharmacokinetic Evaluation ........................................................................................ 42 
12.2 
General Safety .............................................................................................................. 42 
12.2.1 
ECGs ............................................................................................................................ 42 
12.2.2 
Biochemistry ................................................................................................................ 43 
12.2.3 
Hematology .................................................................................................................. 43 
12.2.4 
Troponin Levels ........................................................................................................... 43 
12.2.5 
Other Biomarkers of Cardiac Injury and Inflammation ............................................... 43 
12.3 
Laboratory Certification and Reference Ranges .......................................................... 43 
13 
SAFETY: ADVERSE EVENTS ............................................................................... 45 
13.1 
Definitions.................................................................................................................... 45 


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FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 15 of 61 
13.2 
Relationship to Study Drug .......................................................................................... 45 
13.3 
Intensity of Adverse Events ......................................................................................... 46 
13.4 
Reporting Serious Adverse Events .............................................................................. 46 
14 
STATISTICS .............................................................................................................. 48 
14.1 
Study Design ................................................................................................................ 48 
14.1.1 
General Approach/Considerations ............................................................................... 48 
14.1.2 
Populations ................................................................................................................... 48 
14.1.3 
Study Outcomes ........................................................................................................... 48 
14.1.4 
Sample Size Estimation ............................................................................................... 49 
14.1.5 
Interim and Final Analyses .......................................................................................... 49 
14.1.6 
General Analysis of Safety and Efficacy Outcomes .................................................... 50 
14.1.7 
Pharmacokinetic Data Analysis ................................................................................... 50 
15 
ACCESS TO SOURCE DATA/DOCUMENTS ...................................................... 52 
15.1 
Ethical Conduct of the Study ....................................................................................... 52 
15.2 
Study Monitoring ......................................................................................................... 52 
15.3 
Institutional Review Board (IRB) / Independent Ethics Committee (IEC) ................. 53 
16 
QUALITY CONTROL AND QUALITY ASSURANCE ....................................... 55 
17 
INFORMED CONSENT ........................................................................................... 56 
18 
PROTOCOL DEVIATIONS .................................................................................... 58 
19 
DATA HANDLING AND RECORDKEEPING ..................................................... 59 
19.1 
Reporting and Recording of Data ................................................................................ 59 
19.2 
Retention of Records.................................................................................................... 59 
19.3 
Confidentiality and Publications .................................................................................. 59 
20 
REFERENCES ........................................................................................................... 61 
 


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FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 16 of 61 
LIST OF TABLES 
Table 1: Emergency Contact Information..................................................................................... 12 
Table 2: Study Design and Schedule of Assessments .................................................................. 30 
Table 3: Relationship of AE to Study Drug or Trial-Related Procedures .................................... 45 
 
LIST OF FIGURES 
Figure 1: Study Diagram ............................................................................................................... 29 
 


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FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 17 of 61 
2 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation or Specialist Term 
Explanation 
ACT 
activated clotting time 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AMI 
acute myocardial infarction 
AST 
aspartate transaminase 
AUC 
area under (concentration-time) curve  
BMI 
body mass index 
BP 
blood pressure 
CL 
Clearance 
Cmax 
maximal drug concentration 
CMR 
cardiac magnetic resonance 
CRF 
case report form 
DLT 
dose limiting toxicity 
ECG 
Electrocardiogram 
EDV 
end diastolic volume 
ESV 
end systolic volume 
EF 
ejection fraction 
FS 
fractional shortening 
GCP 
good clinical practice 
GLP 
good laboratory practice 


Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 18 of 61 
Abbreviation or Specialist Term 
Explanation 
GGT 
gamma-glutamyl transferase 
HR 
heart rate 
IB 
investigators brochure 
ICH 
international conference on harmonization 
INF 
infarct size 
IRB 
institutional review board 
IV 
Intravenous 
Kg 
Kilogram 
LAR 
legally appointed representative 
MCH 
mean corpuscular haemoglobin 
MCHC 
mean corpuscular haemoglobin concentration 
MCV 
mean corpuscular volume 
MedDRA 
medical dictionary for regulatory activities 
MI 
myocardial infarction 
mL 
Milliliters 
MSI 
myocardial salvage index 
NOAEL 
no adverse effect level 
OOR 
out of range 
PCI 
percutaneous coronary intervention 
PCV 
packed cell volume 
PI 
principal investigator 
PK 
Pharmacokinetic 
RBC 
red blood cell count 


Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 19 of 61 
Abbreviation or Specialist Term 
Explanation 
RR 
respiratory rate 
SAE 
serious adverse event 
T1/2 
elimination half-life 
Tmax 
time to maximal drug concentration 
V 
volume of distribution 
WCC 
white cell count 
 


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FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 20 of 61 
3 
INTRODUCTION 
3.1 
Disease 
The first line of therapy for STEMI includes coronary artery reperfusion by mechanical means (angioplasty). While clearly effective, 
it does not address the issue of “reperfusion injury”, a secondary damage that develops due to the revascularization of the previously 
ischemic myocardial tissue. Even though angioplasty has dramatically improved the survival rate, the goal of developing FDY-5301 in 
AMI is to reduce infarct size, and consequently improve short and longer-term outcomes after AMI/reperfusion. 
3.2 
FDY-5301 Background 
FDY-5301 product (herein after referred to as FDY-5301) is sodium iodide formulated as an isotonic solution in a single use vial for 
intravenous administration. The solution has a pH between 7.0 and 9.5. A monograph for sodium iodide is listed in the current United 
States Pharmacopoeia (USP). The chemical formula of sodium iodide is NaI.  
The route of administration is by intravenous (IV) injection.  
As discussed in the Investigators Brochure (IB), the nonclinical safety assessment of FDY-5301 includes pilot and Good Laboratory 
Practice (GLP) 7 and 14 day IV repeat dose toxicity studies, pharmacokinetic studies, local tolerability studies, a series of in vitro and 
in vivo safety pharmacology, in vitro hemocompatibility, in vitro cytochrome P450 inhibition, in vitro protein binding, and 
genotoxicity studies conducted in accordance with International Conference on Harmonization (ICH) guidelines. 
An IV bolus single dose toxicity study in rats showed that FDY-5301 was associated with no mortality in animals receiving bolus 
injections of up to 1000 mg/kg. Adverse clinical signs were not observed in either gender. 
In rats, no signs of toxicity were observed at doses up to 74 mg/kg given daily IV for 14 days. In beagle dogs the NOAEL was 
established at 20 mg/kg for 7 days dosing. The observed DLT at 40 mg/kg was reversible gastro-intestinal inflammation.   
Safety pharmacology studies included an in vitro hERG K+ ion channel assay, a CNS safety pharmacology study (general signs and 
behavior) in rats, a pulmonary safety pharmacology study in rats, and a cardiovascular safety pharmacology study in dogs. Overall, the 
results of these studies show that at the dosing regimen and at expected systemic exposures of FDY-5301 to be achieved in humans, 
no adverse effects are anticipated to occur in any of the major organ systems tested.  


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FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
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FDY-5301 was found not to be mutagenic in the bacterial reverse mutation assay.  
Other studies with FDY-5301 show that the formulation to be used for clinical trials is not expected to cause local perivenous 
irritation. In addition, it does not exhibit protein binding nor does it inhibit cytochrome P450 enzymatic activity. FDY-5301 was also 
shown to be compatible with human, dog, and rat serum, plasma, and whole blood. 
As well as the extensive experience and known safety of orally administered iodide, it has been used intravenously in humans to 
manage thyrotoxic crisis. 
Faraday has conducted a phase 1 single ascending dose study in healthy volunteer subjects at intravenous doses of up to 10 mg/kg. No 
significant adverse events were detected, including biochemical measures of thyroid function. The anticipated therapeutic dose is 
likely in the range of 0.5 to 2.0 mg/kg based on nonclinical studies and human PK data. 
3.3 
Rationale 
Preclinical pharmacology data to date show that FDY-5301 when administered in conjunction with the revascularization of previously 
ischemic myocardium significantly reduces infarct size, improves myocardial function and coronary perfusion, reduces neutrophil 
infiltration and down-regulates the inflammatory response in the reperfused myocardial tissue. FDY-5301 may reduce myocardial 
reperfusion injury in patients with AMI undergoing revascularization, and consequently, reduce infarct size. No clinical trials in AMI 
patients have yet been conducted with FDY-5301. The anticipated human effective dose based on preclinical data is from 0.5 to 2.0 
mg/kg. The study outlined herein is designed to assess the safety, efficacy and PK of FDY-5301 in patients with first STEMI about to 
undergo PCI. 


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FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 22 of 61 
4 
TRIAL OBJECTIVES AND PURPOSE 
The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics (PK) of three dose levels of FDY-5301 compared to 
placebo in STEMI patients undergoing PCI. 
4.1 
Primary Outcome 
The primary outcome for this study will be the combined number and incidence rate of several arrhythmias of interest that occur in 
each group over a 14 day period post-study drug. These arrhythmias including ventricular fibrillation, sustained ventricular 
tachycardia (≥125 BPM, ≥ 30 seconds), non-sustained ventricular tachycardia (≥ 125 BPM, ≥ 16 beats, < 30 seconds) and high degree 
AV block ( 2nd or 3rd degree, ≥ 8 beats) were chosen because they are significant prognostic indicators of depressed left ventricular 
ejection fraction and cardiac death [1]. The combined number of arrhythmic events in each group will be calculated along with the 
arrhythmia incidence rate defined as the percentage of patients in each group experiencing at least one of the defined arrhythmias of 
interest.  
An exploratory sub-analysis will be conducted to determine the number and incidence rate of each separate arrhythmia type per dose 
group.  
Continuous cardiac monitoring will occur for 14 days post PCI by means of wearable patch devices. 
4.2 
Secondary Outcomes 
Infarct size parameters will be assessed by CMR at 72 +/- 24 hours and 3 months; the following will be compared between groups; 
infarct size as a proportion of ventricular volume (INF/VV), myocardial salvage index (MSI) and absolute MI size.  
 
• 
The proportion of patients with ST-segment resolution at 4 hours post study drug 
• 
Serum levels of troponin calculated as AUC 0-48 hours post-study drug 
• 
Persistent arrhythmias at 30 days and 3 months 
• 
Measures of cardiac function by CMR including end-diastolic volume (EDV), end-systolic volume (ESV), fractional 
shortening (FS) and ejection fraction (EF). 
 
• 
Serum biomarkers of cardiac injury, inflammation and remodeling 
• 
      Cardiac-related adverse events including the development of heart failure out to 3 months of follow up 
• 
Incidence of all cause and cardiac mortality out to 6 months of follow up-to be assessed by phone call to patient or if 


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Clinical Study Protocol 
 
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Page 23 of 61 
patient is unavailable, by medical records of physician/investigator. 
 
Safety and Tolerability: 
Physical examination including vital signs, laboratory measures to include clinical chemistry, hematology and thyroid function tests 
will be performed. Adverse Events (AEs) and Serious Adverse Events (SAEs) will be recorded.  
12 lead ECGs will be performed at intervals at and post baseline.  
Pharmacokinetics: 
Plasma iodide levels will be measured in each patient. The concentration-time profile of plasma iodide will be derived for each of the 
groups. The pharmacokinetics of iodide will be described as area under the concentration versus time curve (AUC), the maximal 
concentration (Cmax) and the time (Tmax) when the maximal concentration is achieved. The terminal half-life (T1/2), the total body 
clearance (CL), and the volume of distribution (V) will also be derived. 


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Clinical Study Protocol 
 
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5 
INVESTIGATIONAL PLAN 
5.1 
Overall Study Design and Plan: Description 
This is a Phase 2A, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of Intravenous FDY-5301 in Acute 
Myocardial Infarction (AMI).  
Study subjects will be recruited at each investigational site (or referred to the investigative site from another institution) for treatment 
of first STEMI. Subjects will be screened and written informed consent will be obtained prior to initiation of any study related 
procedures in those subjects who meet the inclusion and exclusion criteria for the study. 
Up to 160 patients will be randomized to receive either FDY-5301 at doses of 0.5 mg/kg, 1.0mg/kg, 2.0mg/kg or placebo.  
STEMI diagnosis will be made based on clinical and ECG findings including: subjects presenting with ≥ 30 minutes of ischemic chest 
pain, within 12 hours of symptom onset, and have persistent ST-segment elevation of ≥ 2 mm in at least 2 contiguous leads in ECG.  
  
Study drug administration will occur by bolus injection at any time between an hour and 5 minutes prior to coronary reperfusion. 
All patients who receive study drug and have PCI will be followed up for safety and efficacy for 6 months post-study drug infusion. 
Subjects who do not undergo angioplasty for any reason who received study drug will be followed up for safety, but will be replaced 
with a new subject. 
5.2 
Number of Centers/Subjects 
This study will be conducted at up to 20 centers in the USA and Europe. European sites are not using this version of the protocol and 
will not be submitted to the IND. Up to 160 STEMI patients are planned for enrolment in this study to obtain a final sample size of 80 
patients. 


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5.3 
Estimated Study Duration 
This study is expected to take up to 12 months to complete screening and enrollment for all subjects. Each subject’s participation will 
be up to 6 months from the time of screening to study exit.  
5.4 
Assignment to Study 
Screening numbers will be assigned sequentially at each study site as soon as informed consent has been obtained either by the subject 
or a legally authorized representative of the subject. Information from patients who are screened and do not meet the study entry 
criteria will be entered into a screening log. Once assigned, screening numbers for any screening failures, untreated, non-evaluable, or 
discontinued subjects will not be re-used. 
All subjects who satisfy the Inclusion/Exclusion criteria will be randomly allocated to one of four treatment groups (FDY-5301 0.5 
mg/kg, 1.0 mg/kg, 2.0 mg/kg, or placebo). 
5.5 
Schedule of Assessments 
For each subject, the study will consist of Screening/Treatment (Day 1), evaluations at Day 2 and Day 3, and follow-up visits at 14 
days, 30 days and 3 months, and a telephone call at 6 months (see Figure 1). 
5.5.1 
Screening (Day 1 – Prior to PCI) 
1. Prospective subjects will present to the hospital and will be screened for inclusion in this study if they present with ≥ 30 minutes of 
ischemic chest pain, will be catheterized within 12 hours of symptom onset, and have persistent ST-segment elevation of ≥ 2 mm 
in at least 2 contiguous leads in ECG. They will have the purpose of the study and its procedures and risks explained 
 
Subjects, or their legally appointed representative (LAR), must give written informed consent before any screening procedures can be 
started. During screening the following procedures will be conducted for all subjects if possible to determine study eligibility (some 
medical history may be gathered after treatment if not an exclusion criterion): 
• 
Inclusion/Exclusion criteria will be documented 


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Clinical Study Protocol 
 
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• 
12-lead ECG for STEMI diagnosis 
• 
Demographics (age, gender, smoking status) 
• 
General medical/surgical history (co-morbidities, duration of symptoms, and prior and present therapies) 
• 
Study specific medical/surgical history and concomitant conditions, especially thyroid disorders 
• 
Prior and current medications taken within two weeks prior to study drug administration 
• 
Physical examination  
• 
Vital signs including: temperature, pulse, respiratory rate, blood pressure 
• 
Height and weight: In the event that the body weight is not available at time of study drug dosing, the subject’s last 
reported weight or estimated weight will be used for study drug dosage calculation.  
5.5.2 
Treatment Day 1 – in Cardiac Catheterization Lab and Recovery 
• 
Random allocation to study drug (once screening is complete and consent is obtained either from the subject or a legally 
authorized representative of the subject, randomization must occur to ensure study drug is given by bolus injection between 
an hour prior to and 5 minutes prior to coronary reperfusion, so as to be complete at least 5 minutes prior to reperfusion) 
• 
Study drug administration  
• 
Vital signs (pulse, respiratory rate, blood pressure) will be recorded every 15 minutes after study drug for an hour, then 
hourly for another 4 hours. There is a +/- 10 minute window on all vital sign collections 
• 
Blood sampling to assess anticoagulation during the procedure (INR) 
• 
Documentation of peri-procedural arrhythmias by medical staff by 12-lead ECG 
• 
Continuous ECG monitoring will commence post procedure as soon as the 7 day wearable device can be affixed to the 
patient and up to 14 days post study drug1 
• 
Standard 12 lead ECG prior to treatment to obtain baseline ST-segment elevation and again at 4 hours post-study drug to 
assess ST segment resolution (3 strips at each time point) 
• 
Blood samples for troponin T will be obtained (see time points in Section 12) 
• 
PK blood sampling (see time points in Section 12) 
• 
Blood sample to assess biomarkers of cardiac injury and inflammation (see time points in Section 12) 
• 
Laboratory safety tests (as outlined in Section 12) 
• 
Recording of concomitant medications 
• 
Recording of any AEs 
• 
If study informed consent was given by the subject’s legally authorized representative for study enrollment, the subject will 
be provided with a modified consent once they are stable (after investigational drug treatment and STEMI procedure)  and 


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Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 27 of 61 
in the opinion of the investigator capable of providing written consent.  This modified informed consent document will 
cover the subject’s agreement to remain in the clinical trial and proceed with all study related procedures and follow-up. 
1 The wearable ECG monitor device should be affixed to the patient as soon as possible post-study drug. This single-use device will need to be removed 
when the patient undergoes CMR at 72 +/- 24 hours post-study drug. At that time, a new wearable ECG monitor device will need to be affixed to the 
patient.  
5.5.3 
Day 2 (24 hours +/- 2 hours post-study drug) 
• 
Physical examination and vital signs (pulse, respiratory rate, blood pressure) 
• 
Laboratory safety tests (as outlined in Section 12) 
• 
Blood samples for troponin T will be obtained (see time points in Section 12) 
• 
PK blood sampling (see time points in Section 12) 
• 
Blood sample to assess biomarkers of cardiac injury and inflammation (see time points in Section 12) 
• 
Recording of any AEs 
• 
Concomitant medications 
5.5.4 
Day 3 (48 hours +/- 2 hours post-study drug) 
• 
Physical examination and vital signs (pulse, respiratory rate, blood pressure) 
• 
Laboratory safety tests (as outlined in Section 12)   
• 
Blood samples for troponin T will be obtained (see time points in Section 12) 
• 
Blood sample to assess biomarkers of cardiac injury and inflammation (see time points in Section 12) 
• 
Recording of any AEs 
• 
Concomitant meds 
5.5.5 
First CMR (72 hours +/- 24 hours post-study drug)   
• 
CMR to measure MSI, INF/VV, INF and cardiac function including EDV, ESV, FS and EF. If CMR cannot be completed 
at the time of discharge, the patient should be encouraged to return for a CMR 48-96 hours post-study drug.   
• 
Physical examination and vital signs (pulse, respiratory rate, blood pressure) (at time of discharge) 
• 
Recording of any AEs (at time of discharge) 
• 
Concomitant medications (at time of discharge) 


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Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
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• 
Discharge with instructions for continuous ECG device (at time of discharge)2  
2 Instructions for the wearable ECG monitoring device will be given prior to discharge. The wearable ECG monitoring devices can collect data for 7 
days therefore, a follow up phone call will be conducted 7 days after the wearable ECG monitoring device was first affixed to the patient to ensure 
compliance with removing the wearable ECG monitoring device and replacing it with another one.  Instructions will also be given at that time on 
retaining the first week’s data for return to the clinic at day 14. 
5.5.6 
Follow-up 14 days (+/- 2 days post drug) 
• 
Physical examination and vital signs (pulse, respiratory rate, blood pressure) 
• 
Body weight (kg) 
• 
Laboratory safety tests (as outlined in Section 12) 
• 
Recovery of wearable ECG devices and recordings 
• 
Recording of any AEs  
• 
Concomitant medications 
5.5.7 
Follow-up 30 days (+/- 1 week post drug) 
• 
Physical examination and vital signs (pulse, respiratory rate, blood pressure) 
• 
Body weight (kg) 
• 
Laboratory safety tests (as outlined in Section 12) 
• 
12-lead ECG  including rhythm strip to identify persistent arrhythmias 
• 
Recording of any AEs 
• 
Concomitant medications 
5.5.8 
Follow-up 3 months (+/- 2 weeks post drug) 
• 
CMR to measure MSI, INF/VV, INF and cardiac function including EDV, ESV, FS and EF 
• 
Recording of any AEs 
• 
Concomitant medications 
• 
12-lead ECG including rhythm strip to identify persistent arrhythmias 
• 
Blood sample for analysis of biomarkers of remodeling 


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Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
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5.5.9 
Follow-up 6 months or early termination (+/- 4 weeks post drug) 
Telephone interview with the subject (or relative if subject unable to give history) for incidence of all cause and cardiac mortality. If 
subject is unavailable, then physician/investigator records will be source of mortality documentation if available.  
Figure 1: Study Diagram 
 


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Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
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Table 2: Study Design and Schedule of Assessments 
Activity 
Screening 
Day 1 
Treatment 
Day 1 
Day 2 
(24 +/- 2 
Hrs ) 
Day 3 
(48 +/- 2 
Hrs) 
First CMR 
(72 +/-24 
Hrs) 
Day 7 
 
14 day 
(+/- 2 
days) 
30 day 
(+/- 1 
week) 
3 month  
(+/- 2 
weeks) 
6 month/Early 
Termination 
(+/- 4 weeks) 
Inclusion/Exclusion Criteria, IC14 
X 
 
 
 
 
 
 
 
 
 
Demographics/Medical History  
X 
 
 
 
 
 
 
 
 
 
Physical Examination(including Con 
meds) 
X 
 
X 
X 
X 
 
X 
X 
X 
 
Vital Signs, con meds 
X 
X10 
X 
X 
X 
 
X 
X 
X 
 
Height and Weight 
X 
 
 
 
 
 
 
 
 
 
Safety Laboratory tests 
 
X3 
X 
X 
 
 
X 
X 
 
 
Troponin T 
 
X4 
X 
X 
 
 
 
 
 
 
Randomization, study drug 
 
X 
 
 
 
 
 
 
 
 
ACT during anticoagulation 
 
X 
 
 
 
 
 
 
 
 
Document peri-proc. arrhythmias 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Continuous ECG 
 
 
 
 
 
 
 
 
 
 
Phone call re continuous ECG 
 
 
 
 
 
X 
 
 
 
 
12 lead ECG 
X 
X11 
 
 
 
 
 
X12 
X13 
 
PK-Iodide levels 
 
X5 
X 
X 
 
 
 
 
 
 
Cardiac Biomarkers  
 
X6 
X 
X 
 
 
 
X 
 
CMR 
 
 
 
 
X7 
 
 
 
X 
 
Adverse Events 
X 
X 
X 
X 
X 
 
X 
X 
X 
 


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Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
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Follow up phone call or review of 
physician records for all-cause 
mortality  
 
 
 
 
 
 
 
 
 
X 
Un-blinded Interim Analysis  
 
 
 
 
 
 
X8 
 
X9 
 
3. Safety Lab Sampling for day 1: Pre-study drug, 4 and 12 hours post-study drug   
4. Troponin Sampling for day 1: Pre-study drug, and 12 hours post-study drug    
5. PK Sampling for day 1: Pre-study drug, 2 minutes post-study drug, 1 and 4 hours post-study drug 
6. Biomarker Sampling for day 1: Pre-study drug, 1, 4 and 12 hours post-study drug 
7. CMR should be conducted 48-96 hours post-study drug preferably before patient is discharged from hospital.   
8. Unblinded analysis of CMRs, 14-day arrhythmias, Troponin levels and ST-segment resolution will be conducted by a separate unblinded team at Covance and rest of 
Covance study team, Faraday, Investigators, and 3rd party vendors will not be unblinded to individual patient treatments 
9. Unblinded analysis of CMRs will be conducted by a separate unblinded team at Covance and rest of Covance study team, Faraday, Investigators, and 3rd party 
vendors will not be unblinded to individual patient treatments 
10. Vital signs (pulse, respiratory rate, blood pressure) will be recorded every 15 minutes after study drug for an hour, then hourly for another 4 hours. There is a +/- 10 
minute window on all vital sign collections 
11. 12-lead ECG for day 1: at screening for diagnosis of STEMI for inclusion criteria, and to obtain baseline ST-segment elevation, during PCI treatment to document 
peri-procedural arrhythmias and again at 4 hours post study drug for ST-segment resolution.  3 strips each at screening and 4 hour time point 
12. 12-lead ECG including rhythm strip to identify any persistent arrhythmias  
13. 12-lead ECG including rhythm strip to identify any persistent arrhythmias 
14. Prior to study enrollment written informed consent will be obtained either from the subject or a legally authorized representative of the subject.   If study informed 
consent was given by the subject’s legally authorized representative prior to study enrollment, the subject will be provided with a modified consent once they are stable 
(after investigational drug treatment and STEMI procedure) and in the opinion of the investigator capable of providing written consent.  This modified informed consent 
document will cover the subject’s agreement to remain in the clinical trial and proceed with all study related procedures and follow-up. 
 
 
 


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Clinical Study Protocol 
 
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Page 32 of 61 
6 
SELECTION AND WITHDRAWAL OF SUBJECTS 
The subject or a legally authorized representative must have provided informed consent after the 
nature of the study has been explained and questions addressed. Subjects must meet the 
following criteria to be eligible to participate in the study. 
6.1 
Subject Inclusion Criteria 
2. 18-80 year old male subjects 
3. 18 to 80 year old female subjects who are not of child-bearing potential.  
4. Accepted for Primary PCI with diagnosis of first STEMI, based on clinical and ECG criteria 
(ST-elevation at the J-point in two contiguous leads with the cut-off points: ≥0.2 millivolt 
(mV) in men or ≥0.15 mV in women in leads V2-V3 and/or ≥0.1 mV in other leads), within 
12 hours of symptom onset. 
Written informed consent prior to study participation (either by the subject or a legally 
authorized representative of the subject) 
6.2 
Subject Exclusion Criteria 
1. Previous myocardial infarction 
2. Left bundle branch block (LBBB) 
3. Previous coronary artery bypass graft surgery (CABG) 
4. Major hemodynamic instability or uncontrolled ventricular arrhythmias. 
5. Known contraindication to CMR (e.g. pacemaker) 
6. Patients with known thyroid disease, or known allergy to iodide. 
7. Subjects with past or current renal impairment requiring dialysis 
8. Pregnant or females of child bearing potential 
9. Body weight > 120 kg or Body Mass Index (BMI) > 35 kg/m2 
10. Use of investigational drugs or devices within 30 days prior to enrollment into the study. 
11. Life expectancy of less than 1 year due to non-cardiac pathology 
12. Any clinically significant abnormality identified at the time of screening that in the 
judgment of the Investigator or any sub-Investigator would preclude safe completion of 
the study 
6.3 
Subject Withdrawal Criteria 
Subjects have the right to withdraw from the study at any time and for any reason without 
prejudice to his or her future medical care by the physician or at the Institution. Subjects may 
also be withdrawn from the study at the discretion of the PI. 
Any subject who withdraws consent to participate in the study will be removed from the study. 
Although the subject is not obliged to give his or her reason for withdrawing prematurely from 
the study, the Investigator should make a reasonable effort to ascertain the reasons while fully 
respecting the subject’s rights. 


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Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 33 of 61 
In the interest of the subject, subjects who withdraw consent or are withdrawn from the study by 
the Investigator should be encouraged to complete a follow-up visit (early termination visit) as 
soon as possible and an effort should be made to complete and report the observations as 
thoroughly as possible up to the date of withdrawal. All information should be reported on the 
applicable CRF. 
6.4 
Early Termination Visit 
At any such early termination visit, the procedures scheduled for the six-month follow-up should 
be performed.  


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7 
STUDY TREATMENTS  
7.1 
Description of Study Drug 
FDY-5301 is sodium iodide (chemical formula NaI) administered as an isotonic solution for 
intravenous injection with a concentration of 7.2 mg/mL. The dosage form of FDY-5301 is a 
small volume parenteral solution. The solution has a pH between 7.0 and 9.5. Normal saline will 
be used as placebo. 
7.2 
Concomitant Medications 
For all medications taken during the procedure and after, the medication name, total daily dose, 
route, frequency of dosing and indication for use will be recorded on the concomitant medication 
page in the CRF. 
7.3 
Randomization and Blinding 
Study treatment will consist of FDY-5301 (3 dose levels) or placebo.  
All subjects who fulfill all study eligibility criteria will be randomized to receive one of the 4 
treatments allocated by a computer generated randomization code. Clinical staff will be kept 
unaware of treatment allocation as placebo and active vials will be identical in appearance. 


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8 
STUDY DRUG MATERIALS AND MANAGEMENT 
8.1 
Study Drug 
FDY-5301 will be provided as single use vials for injection containing 20 mL of drug product at 
a concentration of 7.2 mg/mL. The active ingredient sodium iodide (NaI), and the following 
inactive excipients: sodium chloride, and water for injection.  
Placebo will be provided as single use 20 mL vials for injection containing sterile saline solution. 
The manufacturing batch (or box number) of investigational product (active drug, placebo) will 
be recorded on each subject’s drug administration case report form (CSR). 
8.2 
Study Drug Packaging and Labeling 
FDY-5301 final drug product will be manufactured and packaged by Alcami on behalf of 
Faraday Pharmaceuticals, Inc. in accordance with GMP.  
Supply and Return of Drug 
Clinical supplies will be shipped to sites following the completion of study initiation and receipt 
of Institutional Ethics Approval.  
Labels will be in accordance with all applicable local regulations and may include: 
• 
For Investigational Use Only 
• 
Site identification 
• 
Subject Number (blank for insertion) 
• 
Batch (Lot) Number 
• 
Storage conditions 
• 
Expiry Date 
• 
Sponsor’s Name 
8.3 
Study Drug Storage 
Clinical trial materials will be securely stored as supplied (20 to 25 °C) and should not be 
stored frozen. Direct exposure to sunlight and heat should be avoided. 
The sponsor reserves the right to inspect the drug storage area before and during the trial. 
8.4 
Study Drug Preparation 
The formulation has no preservative and is intended for single use only; injection solutions 
should be prepared using aseptic technique and inspected prior to administration. The solution 
for injection should be a clear, colorless solution with no particulate matter.  


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Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 36 of 61 
A guide will provide detailed instructions for randomization and calculation of dose of drug (or 
volume of placebo) and preparation of the intravenous injection.  Drug administration by bolus 
injection to the subject must occur at any time between 60 minutes and 5 minutes prior to 
reperfusion of the coronary artery.  
8.5 
Administration 
FDY-5301 will be administered intravenously by a healthcare professional. Dosage will be 
administered on a body weight basis, according to treatment assignment and using the subject’s 
body weight determined on the dose administration day. Preparation of the administered dose 
will be achieved by adjusting the volume of undiluted solution of 7.2 mg/mL FDY-5301 
8.6 
Study Drug Accountability 
Study drug will only be used for purposes of this study. The clinical site staff will be responsible 
for the study drug accountability, reconciliation and record maintenance in accordance with all 
applicable regulatory requirements. The amount of drug received from Faraday Pharmaceuticals 
and the amount administered to subjects will be documented. 
Investigational Product Accountability 
An investigational product accountability record for the investigational products mandated by the 
protocol must be kept current and should contain: 
• 
The dates and quantities of investigational product received from Faraday 
Pharmaceuticals, Inc. 
• 
manufacturing batch or box numbers for product received 
• 
subject’s identification (subject number and initials) 
• 
date and quantity of investigational product dispensed (and remaining, if from 
individual subject drug units) 
• 
the initials of the dispenser 
• 
date and quantity of drug returned to the investigator/pharmacy, if appropriate 
At the end of the study, the final investigational product reconciliation statement must be 
completed and provided to Faraday Pharmaceuticals. 
These inventories must be made available for inspection by an authorized Faraday 
Pharmaceuticals representative or designee and regulatory agency inspectors.  The investigator is 
responsible for the accountability of all used and unused trial supplies. 
8.7 
Study Drug Handling and Disposal 
Only subjects randomized into the study may receive study drug. Authorized and adequately 
trained staff will administer the study drug.  


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Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 37 of 61 
The Principal Investigator must maintain accurate records demonstrating dates and amount of 
drug received, to whom it was dispensed and accounts of any drug accidentally or deliberately 
destroyed. It will be the responsibility of the Sponsor to ensure that adequate samples of all trial 
doses are retained in accordance with the relevant regulatory guidelines.  
At the conclusion of the trial, a final inventory will be performed by the Sponsor Monitor and the 
Principal Investigator or nominees. If any supplies cannot be accounted for, this should be 
documented on the drug accountability form together with an explanation of the discrepancy. 
The originals of the drug accountability and dispensing logs must be sent to the Sponsor. The 
Principal Investigator will retain copies of these logs on file. 
Any remaining drug at the end of the study will be disposed of as per sponsor instructions (e.g. at 
the site by using approved drug destruction methods). 


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FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 38 of 61 
9 
REPLACEMENT OF SUBJECTS 
Any subject who signs an informed consent form but is not randomized will be considered a 
screen failure and be replaced. Any subject who receives investigational treatment that does not 
undergo PCI will be followed up for safety but replaced.  


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Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 39 of 61 
10 
CMR PROTOCOL 
MRI determination of MSI, MI size, MI/VV, and Cardiac Function 
Cardiac MRI (CMR) will be performed at 72 +/- 24 hours and 3 months post-study drug at the 
study site.  
The 72 hour CMR will include cine, T2W and LGE imaging for function, edema and necrosis 
respectively. The 3 month CMR will include cine and LGE for function and late scar 
quantification respectively. 
The primary estimate of AAR and hence MSI will be based on CMR imaging of myocardium for 
edema (secondarily the length of coronary artery occluded will be document at the time of PCI).  
Cardiac function will be assessed by CMR and defined in terms of EDV, ESV, FS and EF.  
All MRI data will be analyzed at a central core laboratory. Detailed instructions for the conduct 
and interpretation of the CMR will be available in a separate document, including the parameters 
to be analyzed. 


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Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 40 of 61 
11 
STUDY OUTCOMES 
Primary Outcome: 
The primary outcome for this study will be the combined number 
and incidence rate of several arrhythmias of interest that occur in 
each group over a 14 day period post-study drug.  
These arrhythmias including ventricular fibrillation, sustained 
ventricular tachycardia (≥125 BPM, ≥ 30 seconds), non-sustained 
ventricular tachycardia (≥ 125 BPM, ≥ 16 beats, < 30 seconds) and 
high degree AV block ( 2nd or 3rd degree, ≥ 8 beats) were chosen 
because they are significant prognostic indicators of depressed left 
ventricular ejection fraction and cardiac death [1].  
The combined number of arrhythmic events in each group will be 
calculated along with the arrhythmia incidence rate defined as the 
percentage of patients in each group experiencing at least one of 
the defined arrhythmias of interest.  
An exploratory sub-analysis will be conducted to determine the 
number and incidence rate of each separate arrhythmia type per 
dose group.  
Continuous ECG monitoring will occur from post reperfusion until 
14 days post study drug by means of wearable ECG recorders. 
These will be positioned and activated as soon as feasible after 
treatment with study drug is complete. 
Blinded, standardized centralized interpretation will be used for 
analysis of arrhythmias recorded with the wearable device. 
Descriptions of peri-procedural arrhythmias such as reperfusion 
arrhythmias or VF episodes occurring prior to application of the 
wearable cardiac monitor will be categorized and documented 
separately on the CRF, with particular emphasis on persistent 
arrhythmias. 
Secondary Outcomes: 
 Infarct size parameters will be assessed by CMR at 72 +/-
24 hours and at 3 months; the following will be compared 
between groups; infarct size as a proportion of ventricular 
volume (INF/VV), myocardial salvage index (MSI) and 
absolute MI size  
 The proportion of patients with ST-segment resolution at 4 
hours post study drug 
 Serum levels of troponin calculated as AUC 0-48 hours 
post-study drug 


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Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 41 of 61 
 Serum biomarkers of cardiac injury, inflammation and 
remodeling out to 3 months of follow up 
 Persistent arrhythmias at 30 days and 3 months 
 Measures of cardiac function by CMR including EDV, 
ESV, FS and EF 
 Cardiac-related adverse events including the development 
of heart failure out to three months of follow up.  
 
Incidence of all-cause and cardiac mortality out to 6 months of 
follow up 


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Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 42 of 61 
12 
ASSESSMENT OF PHARMACOKINETICS, TROPONIN AND LABORATORY 
SAFETY MEASURES 
12.1 
Pharmacokinetics: Blood Iodide Levels 
12.1.1 
Pharmacokinetic Evaluation 
The concentrations of FDY-5301 will be measured in plasma. 6 mL of blood should be collected 
in a lithium heparin tube. Every effort should be made to collect the PK samples as close to the 
time points listed below. 
• 
Pre-study drug  
• 
2 minutes, 1, 4, 24 and 48 hours post-study drug 
The pharmacokinetic analysis will include calculations of concentration-time profiles in subjects 
following dosing with study drug. Mean, standard deviation (SD) and CV will be calculated at 
each time point. For each dose group, the pharmacokinetic behavior of blood iodide will be 
described as area under the concentration versus time curve (AUC, AUCinf) the maximal 
concentration (Cmax), the time (Tmax) when the maximal concentration is achieved, the apparent 
terminal elimination rate (Kel) and terminal half-life (T1/2) for each subject. From this 
information, the total body clearance (CL), and the volume of distribution (V) will be derived. 
12.2 
General Safety 
Safety and tolerability measurements will include: 
• 
Physical examination 
• 
Vital signs, including monitoring of blood pressure, pulse and heart rate 
• 
Blood samples will be collected for hematology, clinical chemistry, coagulation 
parameters and thyroid function tests 
• 
Adverse events 
12.2.1 
ECGs 
12 lead ECGs will be used to confirm STEMI diagnosis during screening, document peri-
procedural arrhythmias during treatment, obtain baseline ST-segment elevation prior to treatment 
and in order to evaluate ST segment resolution 4 hours post-study drug. In addition, 12 lead 
ECGs will be used to confirm any persistent arrhythmias at the following time points: 
• 
30 days post-study drug 
• 
3 months post-study drug 


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12.2.2 
Biochemistry 
Samples will be analyzed for sodium, potassium, chloride, bicarbonate, glucose, urea, urate, 
creatinine, phosphate, total and, albumin, total protein, total and conjugated bilirubin, GGT, 
alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate transaminase (AST), 
lactate dehydrogenase (LD), TSH, T3 and free T4 at the time points listed below: 
• 
Pre-study drug 
• 
4, 12, 24 and 48 hours post-study drug 
12.2.3 
Hematology 
Samples will be analyzed for ACT (during anticoagulant administration only) hemoglobin, red 
blood cell count (RBC), packed cell volume (PCV), mean corpuscular volume (MCV), mean 
corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), 
platelets, white cell count (WCC), and absolute counts of neutrophils, lymphocytes, monocytes, 
eosinophils and basophils at the time points listed below: 
• 
Pre-study drug 
• 
4, 12, 24 and 48 hours post-study drug 
12.2.4 
Troponin Levels 
In order to calculate AUC 0-48 hours, serum troponin T levels will be measured at the following 
time points: 
• 
Pre-study-drug 
• 
12, 24, 48 hours post-study drug 
12.2.5 
Other Biomarkers of Cardiac Injury and Inflammation 
Serum biomarkers of cardiac injury, inflammation and remodeling will be measured at the 
following time points: 
• 
Pre-study drug  
• 
1,4,12, 24 and 48 hours post-study drug 
• 
3 months post-study drug 
12.3 
Laboratory Certification and Reference Ranges 
Before the initiation of this trial, the Principal Investigator, or nominee, will provide Faraday 
Pharmaceuticals, Inc. with a copy of the certification form, with certification number and 
expiration date for the clinical laboratories used in the trial. Reference ranges for each laboratory 
test used in this trial will be obtained from the relevant laboratory performing trial tests. In the 
event the clinical laboratories are changed during the trial, Faraday Pharmaceuticals, Inc. will be 


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promptly notified of the reason and date of the change and appropriate documentation will be 
submitted to verify the certification of the new laboratory.  
All clinical laboratory tests will be conducted at the investigational site’s local laboratory. All 
accreditation certificates and laboratory reference ranges will be obtained prior to the 
commencement of the trial at the investigational site. 


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13 
SAFETY: ADVERSE EVENTS 
13.1 
Definitions 
An Adverse Event (AE) is defined as any untoward medical occurrence in a subject, or clinical 
investigation subject administered an investigational product (pharmaceutical) and which does 
not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporarily associated with the use of a medicinal (investigational) product, whether or 
not related to the investigational product. A relationship to the investigational product is not 
necessarily proven or implied.  
All adverse events occurring after a dose of investigational product observed by the investigator 
or reported by the subject (whether or not attributed to investigational product), will be reported 
on the case report form.  
Given that this study specifically recruits STEMI patients, the MI itself will not be 
characterized as an AE. 
However, complications arising as a consequence of the MI, for example emergent or 
worsening heart failure, death, or known arrhythmias will be specifically documented as 
adverse events in the CRFs.  
Adverse events will be followed until resolved or considered stable out to 3 months. The only 
serious adverse event that will be tracked longer than 3 months is the incidence of death. All-
cause mortality and cardiac-related mortality will be documented by phone call to the patient at 6 
months.  If the patient is unavailable, then mortality status will be obtained through 
physician/investigator records. The following attributes must be assigned by the investigator:  
description; dates of onset and resolution; severity; assessment of relatedness to investigational 
product, other suspect drugs, and action taken.  The investigator may be asked to provide follow-
up information.  
13.2 
Relationship to Study Drug 
The principal investigator (PI) will classify every AE according to its relationship to study drug 
or trial-related procedures. The categories according to World Health Organization guidelines are 
listed in Table 3. 
 
Table 3: Relationship of AE to Study Drug or Trial-Related Procedures 
Rating Classification Definition 
1 
Probable 
An AE that: 
• 
Occurs at a reasonable time interval after administration of the 


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study drug;  
• 
Follows a known response pattern to the study drug and; 
• 
Cannot be reasonably explained by the known characteristics 
of the patient’s clinical state or by other therapies 
2 
Possible 
An AE that: 
• 
Occurs at a reasonable time interval after administration of the 
study drug;  
• 
Follows a known response pattern to the study drug, but; 
• 
Could have been produced by the patient’s clinical state or by 
other therapies 
3 
Unlikely 
• 
An AE for which sufficient information exists to indicate that 
the etiology is unrelated to the study drug; 
• 
Another etiology is specified 
If the AE is classified as unlikely, the PI should provide a likely cause, other illness, concomitant 
medication, or other. 
13.3 
Intensity of Adverse Events 
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study. The assessment will be based on the investigator’s clinical judgment. The intensity of each 
AE and SAE recorded in the CRF should be assigned to one of the following categories:  
Mild: An event that is easily tolerated by the subject, causing minimal discomfort and not 
interfering with everyday activities.  
Moderate: An event that is sufficiently discomforting to interfere with normal everyday 
activities.  
Severe: An event that prevents normal everyday activities.  
An AE that is assessed as severe should not be confused with a SAE. Severity is a category 
utilized for rating the intensity of an event; and both AEs and SAEs can be assessed as severe. 
13.4 
Reporting Serious Adverse Events 
A serious adverse event is defined as a significant hazard or side effect, regardless of the 
investigator or sponsor’s opinion on the relationship to investigational product. 
A serious adverse event is any untoward medical occurrence that at any dose: 
• 
Results in death 
• 
Is life-threatening  (NOTE: The term "life-threatening" in the definition of "serious" 
refers to an event/reaction in which the patient was at risk of death at the time of the 
event/reaction; it does not refer to an event/ reaction which hypothetically might have 
caused death if it were more severe) 
• 
Requires inpatient hospitalization or results in prolongation of existing hospitalization 


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• 
Results in persistent or significant disability/incapacity 
• 
Is a congenital anomaly/birth defect 
• 
Is a medically important event or reaction 
Medical and scientific judgment should be exercised in deciding whether reporting is appropriate 
in other situations, such as important medical events that may not be immediately life threatening 
or result in death or hospitalization but may jeopardize the subject or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above definition. These 
should also usually be considered serious. Examples of such medical events include cancer, 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in hospitalizations, or the development of drug 
dependency or drug abuse. 
Serious clinical laboratory abnormalities directly associated with relevant clinical signs or 
symptoms should also be reported. 
All SAEs occurring on study must be reported to the medical monitor within 24 hours of 
occurrence. These include SAEs within 30 days of the last investigational product dose and up to 
the last formal follow-up observational period, whichever period is longer. 
The investigator should notify the Institutional Review Board (IRB) of SAEs occurring at the site 
in accordance with local procedures, generally within 72 hours after knowledge of the SAE. 
The sponsor has a legal responsibility to notify the appropriate regulatory authorities about the 
safety of any test drug. Accordingly, prompt notification of any adverse events by investigators 
to the sponsor is required. The reporting of SAEs will be conducted in accordance with 
International Conference on Harmonization (ICH) Good Clinical Practice (GCP) and local 
regulatory guidelines. 
The initial notification will include at least a description of the event, and the subject 
identification. This information should be supported as needed with written copies of hospital 
case reports, autopsy reports, and other documents when applicable on the SAE CRF or the site’s 
standard SAE form. 
All adverse events reported in this study will be coded using MedDRA. Treatment-emergent 
adverse events will be listed and summarized per treatment. 


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14 
STATISTICS 
14.1 
Study Design 
This is a Phase 2A, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of 
Intravenous FDY-5301 in Acute Myocardial Infarction 
14.1.1 
General Approach/Considerations 
Missing observations will be excluded from the analyses; they will not be substituted by 
estimated values. 
Demographics will be tabulated and summarized by descriptive statistics (mean, median, 
standard deviation, range) for continuous data and frequency tables for discrete data. Physical 
examination data from baseline and post-study and medical history data at baseline will be listed. 
All clinical safety and tolerability data will be listed for each subject. Hematology and clinical 
chemistry will be analyzed by group mean and outlier analyses.  Laboratory values outside the 
laboratory’s reference ranges and associated repeat values together with comments as to their 
clinical significance will be listed separately. Adverse event data will be summarized by group, 
visit, severity, and relationship to the study drug. 
All adverse events reported in this study will be coded using MedDRA 19.1  
Standard pharmacokinetic parameters will be calculated for blood iodide levels. 
14.1.2 
Populations 
The safety population includes all subjects who were randomized and received any amount of 
study drug. Subjects who did not receive any study medication will not be included in the safety 
population.  
The intent-to-treat (ITT) population will include subjects who gave informed consent and were 
randomized. This is the “full analysis set” of subjects. Subjects are included in the ITT 
population according to the treatment assigned. 
The per protocol population will be a subset of the ITT population and will include subjects who 
gave informed consent, were randomized, received any amount of study drug, underwent PCI, 
and underwent an MRI at 72 +/-24 hours and 3 months. 
14.1.3 
Study Outcomes 
The primary outcome for this study will be the combined number and incidence rate of several 
arrhythmias of interest that occur in each group over a 14 day period post-study drug. These 
arrhythmias including ventricular fibrillation, sustained ventricular tachycardia (≥125 BPM, ≥ 30 
seconds), non-sustained ventricular tachycardia (≥ 125 BPM, ≥ 16 beats, < 30 seconds) and high 
degree AV block ( 2nd or 3rd degree, ≥ 8 beats) were chosen because they are significant 


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prognostic indicators of depressed left ventricular ejection fraction and cardiac death [1]. The 
combined number of arrhythmic events in each group will be calculated along with the 
arrhythmia incidence rate defined as the percentage of patients in each group experiencing at 
least one of the defined arrhythmias of interest.  
An exploratory sub-analysis will be conducted to determine the number and incidence rate of 
each separate arrhythmia type per dose group.  
Secondary exploratory efficacy outcomes will include: 
Infarct size as a proportion of ventricular volume (INF/VV), the myocardial salvage index 
(MSI), absolute MI size (INF) at 72 +/- 24 hours and 3 months post study drug measured by 
CMR. 
The proportion of patients with ST-segment resolution at 4 hours post study drug. 
Serum levels of troponin calculated as AUC 0-48 hours post study drug. 
Cardiac-related adverse events including the development of heart failure.  
The incidence of all-cause and cardiac mortality out to 6 months post PCI. 
In addition to the measurement of safety and efficacy parameters in this study, serum biomarker 
levels of cardiac injury, inflammation and remodeling will also be assessed.  
14.1.4 
Sample Size Estimation 
Little data exists on the incidence of arrhythmias that occur over an extended period of time 
following AMI and monitoring strategies for this type of assessment have not been optimized in 
a clinical trial setting. The primary goal of our study is to characterize the occurrence of 
arrhythmias in this patient population for 14 days post-AMI and to determine the feasibility of 
using ambulatory patch ECG monitors to capture this data.  These data should be regarded as 
exploratory with the objective of identifying a meaningful clinical end point that can be easily 
measured in future, pivotal studies that are adequately powered to detect differences across 
treatment groups.     
Estimating a drop-out rate of approximately 50%, we will need to enroll up to 160 patients in 
order to obtain a final total sample size of 80 patients. A final sample size of 80 patients will 
provide 80% power to detect a 37% reduction in INF/VV assuming an SD of 10%, a 24% 
increase in MSI assuming an SD of 20% and a 39% reduction in Troponin AUC with an SD of 
60%. Equal variance was assumed among groups with an unbalanced allocation of patients to 
placebo (n=20) and combined FDY-5301 treatment groups (n=60). 
14.1.5 
Interim and Final Analyses 
After the 14 day follow up visit to the clinic, all subjects’ data will be collected and analyzed for: 


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• 
Safety (14-day arrhythmias)  
• 
Early efficacy outcomes including MSI, INF/VV, INF 
• 
Serum troponin AUC 0-48 hours post study drug 
• 
ST-segment resolution by 4 hours post-study drug 
• 
Cardiac function including EDV, ESV, FS and EF 
After the 3 month follow up visit, analysis of the following will occur: 
• 
Early efficacy outcomes including MSI, INF/VV, INF 
• 
Cardiac function including EDV, ESV, FS and EF 
All remaining assessments will be analyzed at the conclusion of the study.  
14.1.6 
General Analysis of Safety and Efficacy Outcomes 
Analysis of the primary safety outcome: characterize the number and incidence rate of serious 
arrhythmias that occur during a 14-day interval in this patient population.  No hypothesis will be 
tested and data will be descriptive in nature only.  A more detailed analysis strategy will be 
outlined in the SAP.  
Analysis of exploratory secondary efficacy outcomes:  For all variables with a continuous 
outcome including infarct size relative to the VV, MSI, absolute MI size, cardiac function, 
biomarkers of cardiac injury and cardiac troponin levels, a single pairwise comparison to analyze 
differences between all three FDY-5301 groups (combined) and placebo will be used. An 
unpaired Student’s T test will be used for the pairwise comparison if the data are normally 
distributed and a Mann-Whitney rank test will be used for nonparametric data. Each group will 
then be tested using a one-way analysis of variance (ANOVA) to obtain a common variance 
followed by a Dunnett’s post-test to separately compare each FDY-5301 dose group to placebo. 
For categorical outcome including ST-segment resolution and incidence of all-cause and cardiac 
related mortality or morbidity, odds ratios comparing each FDY-5301 treatment group with 
placebo will be calculated.  
Physical examination data from baseline, post-study and medical history data at baseline and 
peri-procedural arrhythmia data will be listed by patient. All clinical safety and tolerability data 
will be listed for each subject. Laboratory values will be calculated as group mean data and 
presented in shift tables. Comments as to the clinical significance of out of range values will be 
listed separately. Adverse event data will be summarized by group, visit, severity, and possible 
relationship to the study drug. 
14.1.7 
Pharmacokinetic Data Analysis 
The concentration of iodide in blood (at different time points and doses) will be summarized for 
each group. The pharmacokinetic analysis will include collections of a concentration-time profile 
in subjects following dosing with study drug. Mean, standard deviation (SD) and CV will be 
calculated at each time point. The pharmacokinetic behavior of blood iodide will be described as 


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area under the concentration versus time curve (AUC, AUCinf) the maximal concentration (Cmax), 
the time when the maximal concentration is achieved (Tmax), the apparent terminal elimination 
rate (Kel) and terminal half-life (T1/2) for each subject. From this information, the total body 
clearance (CL), and the volume of distribution (V) will be derived. 


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15 
ACCESS TO SOURCE DATA/DOCUMENTS 
15.1 
Ethical Conduct of the Study 
The study will be conducted according to the principles of the World Medical Association’s 
Declaration of Helsinki and the ICH guidelines for GCP.  Faraday will ensure that the study 
complies with all local, federal or country-specific regulatory requirements. 
The Investigator must ensure the anonymity of all subjects participating in the study. Each 
subject will be assigned a unique subject identification number that should be used on all forms 
associated with the subject’s samples or documents that will be supplied to the Sponsor (or 
CRO) or to any party completing testing on behalf of the Sponsor (e.g., samples for central 
laboratory analyses). Data privacy will be maintained according to local and federal 
requirements and will not be released without the written permission of the subject (or the 
subject’s guardian), except as necessary for monitoring and auditing by Faraday, its designee, the 
FDA or other applicable regulatory authority, or the IRB/IEC. 
All unpublished information concerning the study drug, as well as any information concerning 
the business or operations of Faraday Pharmaceuticals or its affiliates that have been provided by 
or on behalf of the Sponsor to the Principal Investigator and all employees and coworkers 
involved with this study (“Study Personnel”), are confidential and will remain confidential 
information and sole property of Faraday. This includes, without limitation, information 
concerning the clinical indications for the study drug, its formula, methods of manufacture, 
regulatory, marketing and strategic information, and all other scientific, nonclinical or clinical 
data relating to it. Study Personnel must agree to use the information only for the purposes of 
carrying out this study and for no other purpose unless prior written permission is obtained from 
Sponsor’s authorized representative, and not to disclose, or use Sponsor’s confidential 
information for any purpose other than performance of the study. Prior written agreement from 
the Sponsor’s authorized representative must be obtained for the disclosure of any said 
confidential information to other parties. 
 
15.2 
Study Monitoring 
Covance is responsible for ensuring the proper conduct of the study with regard to protocol 
adherence and validity of the data recorded on the CRFs. Subject confidentiality will be 
maintained during this process. 
In accordance with applicable regulations, GCP and Covance standard operating procedures, the 
study monitor will visit the site prior to subject enrollment to review the protocol and data 
collection procedures with site staff. The study monitor will also conduct periodic on-site visits. 
During these on-site visits, the monitor will: 
• 
Review study progress 


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• 
Review study data collected 
• 
Conduct source documentation verification 
Data recorded on subject’s CRF will be source document verified by the study monitor. CRFs 
will be forward to the contracted Data Management group and data entered, verified and 
corrected according to the Statistical Analysis Plan. 
The subjects’ CRFs and supporting documents will be reviewed and confidentiality will be 
maintained at all times. Direct access source data verification (SDV) will occur in this trial. 
Parameters checked for 100% of subjects entered into the trial will include, but not be limited to, 
the following:  
• 
Subject ID number and initials  
• 
Date of birth  
• 
Presence of signed informed consent  
• 
Gender 
• 
Eligibility criteria  
• 
Concomitant medication  
• 
Visit dates  
• 
Adverse events  
• 
Compliance with drug administration  
• 
Key safety variables  
The investigator agrees to allow the study monitor direct access to all relevant study-related 
documents and to set aside time to discuss any relevant findings or issues. 
Study closure will involve the following activities with site staff and investigator(s): 
• 
Return of all study-related material to the sponsor 
• 
Resolution of outstanding data queries 
• 
Accountability, reconciliation and arrangements for unused investigational product 
• 
Review of site study records for completeness 
15.3 
Institutional Review Board (IRB) / Independent Ethics Committee (IEC) 
Federal regulations and the ICH guidelines require that approval be obtained from an IRB/IEC 
prior to participation of human subjects in research studies. Prior to the study onset, the protocol, 
informed consent, advertisements or materials to be used for subject recruitment, and any other 
written information to be provided to the subject must be approved by the IRB/IEC. Any 
amendments to the protocol or informed consent will require review and approval by the 
IRB/IEC before the changes are implemented to the study. Documentation of all IRB/IEC 
approvals and of the IRB/IEC compliance with ICH Guideline E6 will be maintained by the site 
and will be available for review by Faraday or its designee. 


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All IRB/IEC approvals should be signed by the IRB/IEC chairman or designee and must identify 
the IRB/IEC name and address, the clinical protocol by title and/or protocol number, and the date 
that approval and/or a favorable opinion was granted. 
The Principal Investigator or authorized designee is responsible for obtaining continued review 
of the clinical research at intervals not exceeding 1 year or as otherwise specified by the 
IRB/IEC. The Principal Investigator or Sub-Investigator must supply Faraday or its designee 
with written documentation of continued review of the clinical research. 
The IRB/IEC is expected to maintain the confidentiality of the protocol and related information. 


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16 
QUALITY CONTROL AND QUALITY ASSURANCE 
The Investigator must ensure that all trial-related site source data, study-related documents and 
reports will be available, and that the provision of direct access for monitoring and auditing by 
Faraday or its designees will be permitted. In addition, the Investigator must ensure that all trial-
related site source data, study-related documents, and reports will be made available for 
inspection by the appropriate Regulatory Authority and review by the IRB/EC/IEC. 
The Investigator is responsible for notifying Faraday in advance of an impending regulatory 
inspection. He/she may request that Faraday provide support for preparation, if necessary, and is 
required to provide updates on the ongoing activities during the inspection and submit any 
citations/objectionable findings (i.e., FDA 483) and is required to share any follow up responses 
to the outcome. 
Accurate and reliable data collection will be assured by verification and cross-check of the 
eCRFs against the Investigator’s records by the Study Monitor (source document verification). 
The Monitor will also review the Investigator’s drug accountability records to ensure that the 
drug supplies are stored and dispensed appropriately. A comprehensive validation program will 
verify the data and queries will be generated for resolution by the Investigator. Throughout the 
study, Faraday or its designates may review data as deemed necessary. 
 


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17 
INFORMED CONSENT 
 
A written informed consent in compliance with Part 50 of Title 21 of the Code of Federal 
Regulations (CFR), with the Declaration of Helsinki, ICH guidelines, federal and/or local 
regulations, and advance approval by the Institutional Review Board (IRB)/Ethics Committee 
(EC)/Independent Ethics Committee (IEC) shall be obtained from each subject or a legally 
authorized representative of the subject prior to entering the study or performing any unusual or 
non-routine procedure that involves risk to the subject, including washout of any medications. 
The decision of whether to obtain written consent directly from the subject will be determined by 
the investigator.  If, in the opinion of the investigator, the subject is not in a state to fully provide 
written consent, the investigator will obtain written consent from a legally authorized 
representative of the subject. 
Before enrollment, each prospective subject or legally authorized representative of the subject 
will be given a full explanation of the study and be allowed to read the approved informed 
consent form. Once the Principal Investigator or authorized designee is assured that the subject 
or legally authorized representative of the subject understands the implications of participating in 
the study, the subject or legally authorized representative of the subject will be asked to give 
consent to participate in the study by signing the informed consent form. 
 If study informed consent was given by the subject’s legally authorized representative prior to 
study enrollment, the subject will be provided with a modified consent once they are stable (after 
investigational drug treatment and STEMI procedure) and in the opinion of the investigator 
capable of providing written consent.  This modified informed consent document will cover the 
subject’s agreement to remain in the clinical trial and proceed with all study related procedures 
and follow-up. 
 
The consent forms must be dated and retained by the Investigator as part of the clinical trial 
records. The Investigator will not undertake any investigation specifically required for the 
clinical trial until valid consent has been obtained. The terms of the consent and when it was 
obtained must also be documented in the CRF. Each subject will receive a fully-signed copy of 
each consent form that he/she signs for the clinical trial 
The Principal Investigator is responsible for maintaining the originally signed ICF document 
according to record retention requirements. 
If any institution-specific modifications to study-related procedures are proposed or made by the 
site, the consent should be reviewed by the Sponsor and/or its designee, if appropriate, prior to 
IRB/IEC submission. Once reviewed, the consent will be submitted by the Principal Investigator 
or authorized designee to his or her IRB/IEC for review and approval prior to the start of the 
study. If the informed consent form is revised during the course of the study, all actively 


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participating subjects must sign the revised form, unless otherwise indicated, i.e. administrative 
changes. 
 
If subject or subject’s partner, becomes pregnant during their participation in the trial, a separate 
pregnancy informed consent form will be obtained, to follow the pregnancy, any complications, 
and the health of the baby.  The pregnancy consent should be obtained at the time the 
investigator becomes aware of the pregnancy. 


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18 
PROTOCOL DEVIATIONS 
The Principal Investigator or designee must document and explain in the subject’s source 
documentation any deviation from the approved protocol. A deviation from the protocol is an 
unintended and/or unanticipated departure from the procedures and/or processes approved by the 
Sponsor and the IRB/IEC and agreed to by the Principal Investigator. Protocol violations and 
deviations will be documented by the clinical monitor throughout the course of monitoring visits. 
Principal Investigator will be notified of violations and/or deviations in writing by the monitor. 
The IRB/IEC should be notified of all protocol violations and deviations according to IRB/IEC 
reporting requirements.  


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19 
DATA HANDLING AND RECORDKEEPING 
19.1 
Reporting and Recording of Data 
It is the responsibility of the Investigator to record essential information in the medical records in 
accordance with local regulations and requirements. The Investigator is responsible for ensuring 
the accuracy, completeness, legibility and timelines of the data recorded in the eCRF. 
The Principal Investigator agrees to maintain accurate source documentation as part of the case 
histories and to accurately enter this information on to the electronic Case Report Forms 
(eCRFs). These source documents are distinct from the eCRFs and are designed to record all 
observations and other data pertinent to the investigation on each subject.  
The eCRFs will be reviewed and the source documents verified by the study monitor during 
routine monitoring visits, in accordance with the Clinical Monitoring Plan, to ensure that data in 
the eCRFs are accurate and complete. 
19.2 
Retention of Records 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of 
clinical development of the investigational product. These documents should be retained for a 
longer period, however, if required by the applicable regulatory requirements or by an agreement 
with Faraday.  
Faraday will notify the Investigator/institution when the study records are no longer needed. 
If the Investigator withdraws from the study (e.g., relocation, retirement), the records must be 
transferred to a mutually agreed upon designee (e.g., another investigator, IRB). Notice of such 
transfer will be given in writing to Faraday.  
The Investigator must inform Faraday immediately if any documents are lost, to be transferred to 
another facility, or to be transferred to a different owner. 
The Investigator must contact Faraday prior to destroying any records associated with the study. 
19.3 
Confidentiality and Publications 
All clinical trial findings and documents will be regarded as confidential. The Investigator and 
members of his/her research team must not disclose such information without prior written 
approval from the Sponsor. 
The anonymity of participating subjects must be maintained. Subjects will be identified on CRFs 
and other documents by their subject number, initials and/or birth date, not by name and subject 
in accordance with local requirements. Documents not to be submitted that identify the subject 
(e.g., the signed informed consent) must be maintained in confidence by the Investigator.  


Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 60 of 61 
Faraday is committed to the timely communication of data from clinical research trials, 
following the Pharmaceutical Research and Manufacturers of America principles. Where 
possible, authorship will be agreed at the beginning of the study. The authors will form a 
publication committee and this committee will propose and develop appropriate scientific 
manuscripts or abstracts from the study data. Investigators may not present or publish partial or 
complete study results individually. Any manuscript or abstract proposed by the Investigators 
must be reviewed and approved in writing by Faraday before submission for publication. Names 
of all Investigators participating in the study will be included in the publication. The publication 
committee for a study will comprise of authors selected in adherence with the International 
Committee of Medical Journal Editors criteria for authorship. That is, all authors must meet each 
of the following 3 criteria: 
 Substantial contribution to conception and design or acquisition of data, or analysis and 
interpretation of data 
 Drafted the article or revised it critically for important intellectual content 
 Approved the final version for publication 
Members of the study steering committee generally fulfill the authorship criteria through their 
involvement in protocol design and review, monitoring of and sometimes direct involvement 
with recruitment, and thus they will usually be part of the publication committee. If studies are 
multicenter, it may be appropriate to assign group authorship. 
In addition, certain Faraday employees involved in the design and conception of the protocol, 
study management and data analysis and interpretation are qualified authors and will be included 
in the publication committee e.g., the lead physician, statistician and study project manager or 
their equivalents. 
 
. 


Faraday Pharmaceuticals, Inc., 
 
FDY-5301 
Clinical Study Protocol 
 
Confidential, FDY-5301-201-US 
Page 61 of 61 
20 
REFERENCES 
 
1.  Poul Erik Bloch Thomsen, MD; Christian Jons, MD; M.J. Pekka Raatikainen, MD; 
Rikke Moerch Joergensen, MD; Juha Hartikainen, MD; Vesa Virtanen, MD; J. Boland, MD; Olli 
Anttonen, MD; Uffe Jakob Gang, MD; Nis Hoest, MD; Lucas V.A. Boersma, MD; Eivin S. 
Platou, MD; Daniel Becker, MSc; Marc D. Messier, PhD; Heikki V. Huikuri, MD; (2010). Long-
Term Recording of Cardiac Arrhythmias With an Implantable Cardiac Monitor in Patients With 
Reduced Ejection Fraction After Acute Myocardial Infarction The Cardiac Arrhythmias and Risk 
Stratification After Acute Myocardial Infarction (CARISMA) Study. Circulation. 121:1258-
1264. DOI: 10.1161/CIRCULATIONAHA.109.902148 
 
 
 

SAP_003.pdf: 
 
Final v1: 11 July 2018 
 
Page 1 of 24 
STATISTICAL ANALYSIS PLAN 
A Phase 2A, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of 
Intravenous FDY-5301 in Acute Myocardial Infarction 
Statistical Analysis Plan Status: Final v1  
Statistical Analysis Plan Date: 11 July 2018 
Study Drug: FDY-5301 
Sponsor Reference Number: FDY-5301-201 
Covance Study Number: 8358698 
Clinical Phase 2a 
Sponsor:  
Faraday Pharmaceuticals, Inc. 
1616 Eastlake Ave E, Suite 560 
Seattle, WA 98102 
 
Study Site: 
Multiple Sites 
 
 
Sponsor Signatory: 
Lori Siegel, MPH 
Clinical Project Manager  
Faraday Pharmaceuticals, Inc 
Phone: 206-492-5320 
email: LSiegel@FaradayPharma.com 
 
Simon Tulloch, BM Bch 
Chief Medical Officer  
Faraday Pharmaceuticals, Inc 
Phone: 206-899-7004 
email: STulloch@FaradayPharma.com 
 
 


Statistical Analysis Plan  
 
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Covance Study: 8358698 
 
Sponsor Reference: FDY-5301-201 
 
Final v1: 11 July 2018 
 
Page 2 of 24 
1  STATISTICAL ANALYSIS PLAN APPROVAL SIGNATURES 
By signing this page when the Statistical Analysis Plan (SAP) is considered final, the signatories 
agree to the statistical, safety, efficacy, and pharmacokinetic (PK) analyses to be performed for 
this study, and to the basic format of the tables, figures, and listings (TFLs). Once the SAP has 
been signed, programming of the TFLs based upon this document can proceed. Any 
modifications to the SAP and TFLs made after signing may result in a work-scope change. 
Covance approval: 
 
 
 
 
Gabriel Lau, MSc 
Statistician 
 
Date 
 
 
 
 
Sarah Thorn, BS 
Pharmacokineticist 
 
Date 
 
Sponsor approval: 
 
 
 
 
Lori Siegel, MPH 
Clinical Project Manager 
 
Date 
 
 
 
 
 
Simon Tulloch, BM, BCh 
Chief Medical Officer 
 
Date 


Statistical Analysis Plan  
 
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Covance Study: 8358698 
 
Sponsor Reference: FDY-5301-201 
 
Final v1: 11 July 2018 
 
Page 3 of 24 
2  TABLE OF CONTENTS 
1 
STATISTICAL ANALYSIS PLAN APPROVAL SIGNATURES ................................... 2 
2 
TABLE OF CONTENTS ................................................................................................... 3 
3 
ABBREVIATIONS ............................................................................................................ 5 
4 
INTRODUCTION .............................................................................................................. 7 
5 
STUDY OBJECTIVE AND PURPOSE ............................................................................ 7 
6 
STUDY DESIGN ............................................................................................................... 7 
6.1 
Primary Outcomes ....................................................................................................... 7 
6.2 
Secondary Outcome ..................................................................................................... 8 
6.2.1 
Secondary Efficacy Outcome ............................................................................. 8 
6.2.2 
Secondary Safety Outcome ................................................................................ 8 
6.2.3 
Secondary Pharmacokinetic Outcome ................................................................ 9 
6.3 
Exploratory Outcome ................................................................................................... 9 
7 
STUDY DESIGN ............................................................................................................... 9 
8 
TREATMENTS ................................................................................................................ 10 
9 
SAMPLE SIZE JUSTIFICATION ................................................................................... 10 
10 DEFINITION OF ANALYSIS POPULATIONS ............................................................ 10 
11 STATISTICAL METHODOLOGY ................................................................................. 11 
11.1 General ....................................................................................................................... 11 
11.1.1 Definition of Baseline and Change from Baseline ........................................... 11 
11.1.2 Repeat and Unscheduled Readings .................................................................. 12 
11.2 Demographics, Patient Disposition, and Baseline Characteristic .............................. 12 
11.3 Previous and Concomitant Medications .................................................................... 12 
11.4 Safety and Efficacy Assessment ................................................................................ 12 
11.4.1 Primary Analysis (Safety) ................................................................................ 13 
11.4.2 Secondary Efficacy Analysis ............................................................................ 14 
11.4.3 Exploratory Analysis (Safety) .......................................................................... 17 
11.5 Safety and Tolerability Assessments ......................................................................... 18 
11.5.1 Adverse Events ................................................................................................. 18 
11.5.2 Clinical Laboratory Parameters ........................................................................ 18 
11.5.3 Vital Signs ........................................................................................................ 18 
11.5.4 Incidence of Mortality ...................................................................................... 19 
11.5.5 Other Safety Assessments ................................................................................ 19 
11.5.6 Safety and Tolerability Statistical Methodology .............................................. 19 
11.6 Pharmacokinetic Assessment ..................................................................................... 19 
11.6.1 Pharmacokinetic Analysis ................................................................................ 19 


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11.6.2 Criteria for Handling Concentrations Below the Limit of Quantification in 
Pharmacokinetic Analysis ................................................................................ 21 
11.6.3 Criteria for the Calculation of an Apparent Terminal Elimination Half-Life .. 21 
11.6.4 Calculation of AUC .......................................................................................... 22 
11.6.5 Anomalous Values ........................................................................................... 22 
11.6.6 Presentation of Pharmacokinetic Data ............................................................. 22 
11.6.7 Pharmacokinetic Statistical Methodology ........................................................ 23 
11.6.8 Pharmacokinetic/Efficacy Analysis ................................................................. 23 
12 INTERIM ANALYSES .................................................................................................... 23 
13 CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES ....... 24 
14 DATA PRESENTATION ................................................................................................ 24 
14.1 Insufficient Data for Presentation .............................................................................. 24 
15 REFERENCES ................................................................................................................. 24 
 


Statistical Analysis Plan  
 
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Page 5 of 24 
3  ABBREVIATIONS 
Abbreviations pertain to the SAP only (not the TFLs). 
ADaM 
analysis data model 
AE 
adverse event 
AMI 
acute myocardial infarction 
ANOVA 
analysis of variance 
ATC 
Anatomical Therapeutic Chemical 
AUC 
area under the curve 
AUCinf 
area under the concentration-time curve extrapolated to infinity 
AUClast 
area under the concentration-time curve from time 0 to the time of the 
last observed quantifiable concentration 
AV 
Atrioventricular 
BLQ 
below the limit of quantification 
BPM 
beats per minute 
CDISC 
Clinical Data Interchange Standards Consortium 
CL 
total body clearance 
Cmax 
maximum observed plasma concentration 
CMR 
cardiac magnetic resonance 
CRF 
Case Report Form 
CSR 
Clinical Study Report 
CV% 
coefficient of variation 
ECG 
electrocardiogram 
EDV 
end-diastolic volume 
EF 
ejection fraction 
ESV 
end-systolic volume 
FS 
fractional shortening 
ICH 
International Conference on Harmonisation 
INF 
infarct size 
ITT 
intent-to-treat 


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Kel 
apparent terminal elimination rate constant 
LLOQ 
lower limit of quantification 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
MSI 
myocardial salvage index 
NC 
not calculated 
NR 
no result 
PCI 
percutaneous coronary intervention 
PK 
pharmacokinetics 
PP 
per protocol 
SAP 
Statistical Analysis Plan 
SD 
standard deviation 
STEMI 
ST-segment elevation myocardial infarction 
T1/2 
apparent terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
TFLs 
tables, figures, and listings 
Tlast 
time of last quantifiable concentration 
Tmax 
time when maximal concentration is achieved 
Vss 
volume of distribution at steady-state 
VV 
ventricular volume 
Vz 
volume of distribution during the terminal elimination phase 
WHO 
World Health Organization 


Statistical Analysis Plan  
 
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Final v1: 11 July 2018 
 
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4  INTRODUCTION 
This SAP has been developed after review of the clinical study protocol Final Version 1.0 dated 
02 April 2017 and Final Version 2.0 dated 21 August 2017. 
This SAP describes the planned analysis of the safety, efficacy, and PK data from this study. A 
detailed description of the planned TFLs to be presented in the Clinical Study Report (CSR) is 
provided in the accompanying TFL shell document. In general, the analyses are based on 
information from the protocol, unless they have been modified by agreement between Faraday 
Pharmaceuticals and Covance Early Clinical Biometrics. A limited amount of information 
concerning this study (eg, objectives, study design) is given to help the reader’s interpretation. 
This SAP must be finalized prior to the lock of the clinical database for this study. When the 
SAP and TFL shells are agreed upon and finalized, they will serve as the template for this 
study’s CSR. 
This SAP supersedes the statistical considerations identified in the protocol; where 
considerations are substantially different, they will be so identified. If additional analyses are 
required to supplement the planned analyses described in this SAP, they may be performed and 
will be identified in the CSR. Any substantial deviations from this SAP will be agreed upon 
between Faraday Pharmaceuticals and Covance Early Clinical Biometrics and identified in the 
CSR. 
This SAP is written with consideration of the recommendations outlined in the International 
Conference on Harmonisation (ICH) E9 guideline entitled, “Guidance for Industry: Statistical 
Principles for Clinical Trials” and the ICH E3 guideline entitled, “Guidance for Industry: 
Structure and Content of Clinical Study Reports.”1,2 
5  STUDY OBJECTIVE AND PURPOSE 
The purpose of this study is to evaluate the safety, efficacy, and PK of 3 dose levels of 
FDY-5301 compared to placebo in ST-segment elevation myocardial infarction (STEMI) 
patients undergoing percutaneous coronary intervention (PCI).  
6  STUDY DESIGN 
6.1 
Primary Outcomes 
The primary outcome for this study will be the combined number and incidence rate of several 
arrhythmias of interest for 14 days post-study drug. The arrhythmias of interest include the 
following categories:  
 
 Ventricular fibrillation  
 Sustained ventricular tachycardia (heart rate [HR] ≥125 beats per minute [BPM], ≥ 
30 seconds) 


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 Non-sustained ventricular tachycardia (HR ≥125 BPM, ≥ 16 irregular beats, < 30 seconds)  
 High degree Atrioventricular (AV) block (2nd or 3rd degree, ≥ 8 irregular beats)  
The time-to-last-event outcome for each arrhythmia of interest will be studied.  
The time-to-patch-applied, derived as time duration between the start of PCI procedure and the 
application of the patch monitoring device will also be studied. 
6.2 
Secondary Outcome 
6.2.1 Secondary Efficacy Outcome 
The secondary efficacy outcomes for this study will be: 
 Infarct size parameters assessed by CMR at 72 ±4 hours post-study drug and 3 months 
post-study drug 
o Infarct size as a proportion of ventricular volume (INF/VV) 
o Myocardial salvage index (MSI)  
o Absolute myocardial infarction size (INF).  
 Proportion of patients with ST-segment resolution at 4 hours post-study drug 
 Proportion of patients with persistent arrhythmias at 30 days and 3 months post-study drug 
 Measures of cardiac function by CMR at discharge (72 ± 24 hours) and 3 months for the 
following  
o End-diastolic volume (EDV) 
o End-systolic volume (ESV) 
o Fractional shortening (FS)  
o Ejection fraction (EF)  
 Serum levels of troponin calculated as AUC over 48 hours post treatment 
  Plasma biomarkers of cardiac injury, inflammation and remodeling out to 3 months of 
follow up 
6.2.2 Secondary Safety Outcome 
The secondary safety outcomes for this study will be: 


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 Incidence of adverse events (AEs) 
 Change from baseline in physical examination results, clinical laboratory values, and vital 
signs values 
 Incidence of all cause and cardiac mortality out to 6 months of follow up-to be assessed by 
phone call to patient or if patient is unavailable, by medical records of 
physician/investigator 
6.2.3 Secondary Pharmacokinetic Outcome 
Plasma concentrations of iodide will be assessed and the appropriate PK parameters calculated. 
6.3 
Exploratory Outcome 
The exploratory outcome for this study will be: 
 Incidence of newly onset atrial fibrillation during 14 days post-study drug monitoring 
period 
7  STUDY DESIGN 
This is a Phase 2A, randomized, double-blind, placebo-controlled, multi-center study that will 
evaluate the safety, efficacy, and PK of FDY-5301 in patients with acute STEMI undergoing 
PCI.  
Patients will receive either FDY-5301 or volume matched placebo after informed consent is 
obtained and a STEMI diagnosis has been made based on clinical and electrocardiogram (ECG) 
findings, within an hour prior to myocardial reperfusion.  
A minimum of 80 evaluable patients will be enrolled and randomized in a 1:1:1:1 ratio to receive 
a single dose of 0.5, 1.0, or 2.0 mg/kg FDY-5301 or placebo.  
All patients will have an early and late (3 month) cardiac magnetic resonance (CMR) and 14 
days of arrhythmia monitoring and will be followed up for safety and efficacy for up to 6 
months. Patients will be monitored in hospital, and return for clinic visits 14 days, 30 days, and 3 
months post PCI (Figure 1).  
Figure 1: Study Diagram 
 


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Final v1: 11 July 2018 
 
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8  TREATMENTS 
The following is a list of the study treatment abbreviations and ordering that will be used in the 
TFLs. 
Study Treatment Name 
Treatment Order on TFLs 
Placebo 
1 
0.5 mg/kg FDY-5301  
2 
1.0 mg/kg FDY-5301  
3 
2.0 mg/kg FDY-5301  
4 
Overall FDY-5301 
5 (where necessary) 
9  SAMPLE SIZE JUSTIFICATION 
As this is the first clinical study of FDY-5301 in patients, safety is the primary focus. For this 
reason, the goal is to expose a limited number of patients to FDY-5301 while still powering the 
study to detect significant differences in efficacy measures across groups. A total sample size of 
80 patients will provide 80% power to detect a 37% reduction in infarct size (INF) / ventricular 
volume (VV) assuming a standard deviation (SD) of 10%, a 24% increase in MSI assuming a SD 
of 20% and a 39% reduction in Troponin area under the curve (AUC) with an SD of 60%. Equal 
variance was assumed among groups with an unbalanced allocation of patients to placebo 
(n = 20) and overall FDY-5301 treatment groups (n = 60). 
10  
DEFINITION OF ANALYSIS POPULATIONS 
The Intent-to-treat (ITT) population will include patients who gave assent, full consent, 
abbreviated consent or waived consent and were randomized. This is the “full analysis set” of 
patients. Patients are included in the ITT population according to the treatment assigned. 
The Safety Population will consist of all patients who received at least 1 dose of study drug 
(FDY-5301 or Placebo) and have at least 1 postdose safety assessment. 
The Per Protocol (PP) population will be a subset of the ITT population and will include 
patients who gave informed assent/consent, were randomized, received any amount of study 
drug, underwent PCI, and underwent magnetic resonance imaging (MRI) at 72 ±24 hours and 
3 months. 
The PK Population will consist of all subjects dosed with FDY-5301 and have at least 1 
quantifiable postdose PK concentration. 


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The PK/PP Population will consist of all subjects who satisfy the criteria for both the PK and 
PP population. 
All protocol deviations that occur during the study will be considered prior to database lock for 
their severity/impact and will be taken into consideration when patients are assigned to analysis 
populations. Details of patient assignment to the analysis populations will be listed. 
11  
STATISTICAL METHODOLOGY 
11.1 
General 
Data listings will be provided for the ITT Population. Summary statistics and statistical analyses 
will be performed for patients included in the relevant analysis populations. 
For continuous data, summary statistics will include the arithmetic mean, arithmetic standard 
deviation, median, minimum, maximum, and number. For log-normal data (eg, the PK 
parameters: AUCs and maximum observed concentration [Cmax]), the geometric mean and 
geometric coefficient of variation (CV%) will also be presented. For categorical data (i.e. ST-
segment resolution and persistent arrhythmias), frequency counts, percentages and odds ratios 
will be presented, where applicable. Data listings will be provided for all patients up to the point 
of withdrawal, with any patients excluded from the relevant population highlighted. For the 
calculation of summary statistics and statistical analysis, unrounded data will be used. 
Missing values will not be imputed. 
Data analysis will be performed using SAS® Version 9.4 or higher. 
Analysis Data Model (ADaM) datasets will be prepared using Clinical Data Interchange 
Standards Consortium (CDISC) ADaM Version 2.1, and CDISC ADaM Implementation Guide 
Version 1.1. Pinnacle 21 Community Validator Version 2.1.2 will be utilized to ensure 
compliance with CDISC standards. 
11.1.1 Definition of Baseline and Change from Baseline 
Baseline for each parameter is defined as the last value measured prior to dosing, including 
repeat vital signs and unscheduled (clinical laboratory parameters) readings (see Section 11.1.2 
for definitions of repeat and unscheduled readings).  
Mean change from baseline is the mean of all individual patients’ change from baseline values. 
Each individual change from baseline will be calculated by subtracting the individual patient’s 
baseline value from the value at the timepoint. The individual patient’s change from baseline 
values will be used to calculate the mean change from baseline using a SAS procedure such as 
Proc Univariate. 


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11.1.2 Repeat and Unscheduled Readings 
Repeat readings are labelled as ‘Repeat’ in the listings and replace the original readings in all 
summaries and changes from baseline presentations and calculations. Prior to dosing, all 
readings taken in addition to the original reading are defined as predose repeats. Postdose repeat 
readings are defined as readings collected within 15 minutes of the actual time of the original 
reading.  
All results not taken at a scheduled timepoint for other data types (eg, clinical laboratory 
parameters) are unscheduled. Unscheduled readings are labelled as ‘Unscheduled’ in the listings. 
Because unscheduled readings are not associated with any scheduled timepoint, they are 
excluded from all summaries (with the exception that they may be used as baseline, as stated in 
Section 11.1.1). 
11.2 
Demographics, Patient Disposition, and Baseline Characteristic 
The demographic variables age, sex, race, ethnicity, body weight, height, and body mass index 
will be summarized and listed. Patient disposition will be summarized and listed. 
Selected details from the primary PCI procedure will be summarized and all data will be listed.  
Medical history will be summarized by Medical Dictionary for Regulatory Activities (MedDRA) 
system organ class and preferred term for each treatment group, respectively. This data will also 
be listed. 
Important and non-important protocol deviations and the patient assignment to analysis 
populations will be listed. 
11.3 
Previous and Concomitant Medications 
Any medication which started and ended prior to the start of study drug dosing will be 
considered as a previous medication. Concomitant medications are medications that are present 
before the study drug dosing but which were either stopped after the study drug dosing, or 
ongoing during study and medications that were started on or after the study drug administration. 
The previous and concomitant medications will be summarized by preferred term and World 
Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) codes for each treatment 
group. Primary PCI medications will not be coded or summarized. 
All previous and concomitant medications (including primary PCI medications) will be listed. 
11.4 
Safety and Efficacy Assessment 
All analyses under this section will be performed using the ITT population and also repeated 
with the PP population. 


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11.4.1 Primary Analysis (Safety) 
Incidence Rate of Events 
The primary outcome for this study will be the combined number and incidence rate of several 
arrhythmias of interest for 14 days post-study drug. The combined number of arrhythmic events 
in each treatment group will be calculated along with the arrhythmia incidence rate defined as 
the number of arrhythmia events of interest divided by the total person-time within each 
treatment group (or the overall FDY-5301 group), expressed as a percentage. The summarization 
will be presented by 2 separate periods within the 14-day monitoring duration, and also as 
overall. Period 1 will be the first 48 hours since the start of PCI and period 2 will be the 
remaining time of 14-day monitoring duration. 
The same summarization method will be repeated after stratification of baseline TIMI flow 
(grade 1 and lower combined, or, grade 2 and 3 combined) and infarct type (anterior or other). 
Person-time is an estimate of the time-at-risk in hours for all patients who contributed to the 
analysis population. The total person-time is calculated as the sum of recording time across 
patients during the 14 day monitoring period, within each treatment group (or the overall 
FDY-5301 group). The unit for person-time in this study is person-hours. 
The number of arrhythmias of interest and its incidence rates will be summarized by treatment 
group and the overall FDY-5301 group. 
The incidence rate ratio of each active treatment group (and overall) against the placebo group 
will be calculated. 
As an exploratory sub-analysis, the summarization for the number of events and incidence rates 
will be repeated separately for each arrhythmia category as outlined in Section 6.1 and also 
separately for non-serious arrhythmias (ie, any arrhythmias which do not meet the criteria as 
outlined in Section 6.1). 
The arrhythmia incidence rates (ie, arrhythmias per person-time) for each arrhythmia type will be 
summarized by treatment groups in hourly intervals. The intervals may be altered upon 
reviewing the actual data. Arrhythmia rates by time interval may also be presented in a graphical 
format. 
Occurrence of reperfusion arrhythmias collected prior to use of the continuous rhythm 
monitoring device will be summarized according to categories as defined in the CRF. 
Relationship between each arrhythmia type occurred within 48 hours of the start of PCI 
procedure and all-cause mortality may be evaluated depending on data availability. 
Time-to-Last-Event 


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The time-to-last-event is defined as the duration between the start time of PCI and the last 
occurrence of the arrhythmia event. The time-to-event will be censored for a subject if a subject 
does not experience any arrhythmias of interest before the end of the 14-day monitoring period 
or the date of early termination from the study. The censoring time will be at the last available 
time of arrhythmia monitoring. 
Median and first and third quartiles of the time-to-last-event will be summarized for each 
treatment group and the overall FDY-5301 group for each arrhythmia of interest (and combined). 
Kaplan-Meier curves will be presented by treatment, baseline TIMI flow, and infarct type for 
each arrhythmia of interest and also repeated separately for each arrhythmia category. 
Time-to-Patch-Application 
The duration between the start of PCI to the application of the patch will be derived and 
summarized by treatment group.  
 
11.4.2 Secondary Efficacy Analysis 
11.4.2.1 Infarct Size Parameters from CMR  
INF/VV, MSI, and INF will be assessed by CMR at 72 ±24 hours post-study drug and 3 months 
post-study drug. Summary statistics for the observed values along with changes from baseline 
will be produced for each treatment group and the overall FDY-5301 group for each parameter. 
The baseline is defined as the measurement taken at the 72 hour timepoint. 
For the changes from baseline for each of these parameters, a single pairwise comparison will be 
performed to analyze the results between all three FDY-5301 groups (overall) and placebo at 
both the 3 months post-study drug timepoints. An unpaired Student’s T-test will be used for the 
pairwise comparison if the data are normally distributed and a Mann-Whitney rank test will be 
used for nonparametric data. Normality will be assessed based on the Shapiro-Wilk test at the 
5% level. If the unpaired Student’s T-test was selected, the difference in means and its 95% 
confidence interval will be produced.  
Each treatment group will also be tested using a one-way analysis of variance (ANOVA) to 
obtain a common variance followed by a Dunnett’s post-test to separately compare each 
FDY-5301 dose group to placebo. 
The same summarization method and statistical analyses will be repeated by baseline TIMI flow 
(grade 1 and lower, or, grade 2 and 3) and infarct type (anterior or other). 
The changes from baseline in infarct size parameters may be compared between treatment 
groups in the form of a frequency table as necessary. The definition for these changes from 
baseline categories will be determined at a later stage based on the actual data.  


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11.4.2.2 Proportion of Patients with ST-segment Resolution at 4 hours Post-study Drug 
12-lead ECGs will be used to obtain baseline ST-segment elevation prior to treatment in order to 
evaluate ST-segment resolution 4 hours post-study drug. 
ST-segment resolution will be defined as a reduction of the ST-segment elevation by 50% when 
compared to the baseline. Evaluation of the percentage of ST-segment resolution will be 
undertaken on the single worst ECG lead (defined as the lead with the maximal ST-segment 
elevation). Baseline is defined as the maximal ST-segment elevation obtained at Day 1 
screening. Results will be categorized as either resolved or non-resolved. 
The number of patients with ST-segment resolution will be tabulated by treatment group. Odds 
ratios will be calculated for each FDY-5301 treatment group (and overall) against the placebo 
group, along with its 95% confidence interval. 
The same summarization method and statistical analyses will be repeated by baseline TIMI flow 
(grade 1 and lower, or, grade 2 and 3) and infarct type (anterior or other). 
Clinician’s ECG interpretation collected from the eCRFs will be listed. 
11.4.2.3 Persistent Arrhythmias at 30 Days and 3 Months  
12-lead ECGs will be used to confirm any persistent arrhythmias at 30 days and 3 months post-
study drug. 
Assessments of persistent arrhythmias will be listed and the number of subjects with persistent 
arrhythmias will be tabulated by treatment group at 30 days and 3 months. Odds ratio will be 
calculated for each FDY-5301 treatment group against the placebo group, along with its 95% 
confidence interval. 
The same summarization method and statistical analyses will be repeated by baseline TIMI flow 
(grade 1 and lower, or, grade 2 and 3) and infarct type (anterior or other). 
11.4.2.4 Measures of Cardiac Function by CMR  
The EDV, ESV, FS and EF will be assessed at 72 ±24 hours post-study drug and 3 months post-
study drug.  
Summary statistics will be produced for the observed values along with changes from baseline 
by each treatment group and the overall FDY-5301 group for each parameter. The baseline is 
defined as the measurement taken at the 72 hour timepoint. 
For the changes from baseline for each of these parameters, a single pairwise comparison will be 
performed to analyze the results between all three FDY-5301 groups (overall) and placebo. An 
unpaired Student’s T-test will be used for the pairwise comparison if the data are normally 


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distributed and a Mann-Whitney rank test will be used for nonparametric data. Normality will be 
assessed based on the Shapiro-Wilk test at the 5% level. If the unpaired Student’s T-test was 
selected, the difference in means and its 95% confidence interval will be produced. 
The parameters from each group will then be tested using a one-way ANOVA to obtain a 
common variance followed by a Dunnett’s post-test to separately compare each FDY-5301 dose 
group to placebo. 
The same summarization method and statistical analyses will be repeated by baseline TIMI flow 
(grade 1 and lower, or, grade 2 and 3) and infarct type (anterior or other). 
11.4.2.5 Serum Levels of Troponin 
The troponin AUC0-48 will be derived from the serum levels of troponin collected at the 
following timepoints: Predose, 4, 12, 24 and 48 hours post-study drug. AUC0-48 will be 
calculated using the linear trapezoidal method. Where possible, the derivation will be carried out 
using actual post-dose times recorded. If actual times are missing, nominal times may be used 
with sponsor approval. 
Summary statistics (also including geometric means and geometric coefficient of variation 
[CV] %) for the serum levels will be produced by each treatment group and the combined 
FDY-5301 group for the derived AUC0-48. The summary statistics for troponin AUC0-48 will be 
presented in a similar way. 
The derived AUC0-48 will be logarithmically transformed, and an unpaired Student’s T-test will 
be used analyze its differences between all three FDY-5301 groups (overall) and placebo.  
The logarithmically transformed AUC0-48 from each group will then be tested using a one-way 
ANOVA to obtain a common variance followed by a Dunnett’s post-test to separately compare 
each FDY-5301 dose group to placebo.  
The arithmetic least squares means of the treatment differences will be back-transformed to 
provide the geometric means and its 95% confidence interval. 
The same summarization and statistical analyses will be repeated by baseline TIMI flow (grade 1 
and lower, or, grade 2 and 3) and infarct type (anterior or other). 
11.4.2.6 Plasma Biomarkers of Cardiac Injury, Inflammation, and Remodeling 
The plasma biomarker Cmax and AUC0-48 will be derived from the plasma biomarker levels 
collected at the following timepoints: Predose, 1, 4, 12, 24 and 48 hours post-study drug. 
AUC0-48 will be calculated using the linear trapezoidal method. Where possible, the derivation 
will be carried out using actual post-dose times recorded. If actual times are missing, nominal 
times may be used with sponsor approval. Maximum deviation defined as the largest magnitude 
shift (or absolute change) from baseline will be derived. 


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Summary statistics (also including geometric means and geometric CV%) for each plasma 
biomarker concentration will be produced by each treatment group and the overall FDY-5301 
group for the values and its changes from baseline. The baseline is defined as the last actual 
value obtained prior to study drug infusion.  
For each of these plasma biomarker concentrations, a single pairwise comparison will be 
performed by timepoint to analyze change from baseline value between all three FDY-5301 
groups (overall) and placebo. An unpaired Student’s T-test will be used for the pairwise 
comparison if the data are normally distributed and a Mann-Whitney rank test will be used for 
nonparametric data. Normality will be assessed based on the Shapiro-Wilk test at the 5% level.  
Each group will then be tested using a one-way ANOVA to obtain a common variance followed 
by a Dunnett’s post-test to separately compare each FDY-5301 dose group to placebo. 
The logarithmically transformed Cmax, AUC0-48 and maximum deviation from each group will be 
tested using a one-way ANOVA to obtain a common variance followed by a Dunnett’s post-test 
to separately compare each FDY-5301 dose group to placebo.  
The arithmetic least squares means of the treatment differences will be back-transformed to 
provide the geometric means and its 95% confidence interval. 
The same summarization and statistical analyses for plasma biomarker concentrations and 
parameters will be repeated by baseline TIMI flow (grade 1 and lower, or, grade 2 and 3) and 
infarct type (anterior or other). 
11.4.3 Exploratory Analysis (Safety) 
Incidence Rate of New Onset Atrial Fibrillation 
The exploratory outcome for this study will be the combined number and incidence rate of new 
onset atrial fibrillation for 14 days post-study drug. The combined number of events in each 
treatment group will be calculated along with incidence rate defined as the number of events 
divided by the total person-time within each treatment group (or the overall FDY-5301 group), 
expressed as a percentage.  
The number of new onset atrial fibrillation and new onset atrial fibrillation incidence rates will 
be summarized by treatment group and the overall FDY-5301 group. 
The incidence rate ratio of each active treatment group (and overall) against the placebo group 
will be calculated. 
The summarization will be presented by 2 separate periods within the 14-day monitoring 
duration, and also as overall. Period 1 will be the first 48 hours since the start of PCI procedure 
and period 2 will be the remaining time of 14-day monitoring duration. 


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11.5 
Safety and Tolerability Assessments 
All safety analyses will be performed with the safety population. 
11.5.1 Adverse Events 
The study specifically recruits STEMI patients; therefore the myocardial infarction (MI) itself 
will not be characterized as an AE. However, complications arising as a consequence of the MI, 
for example, an emergent or worsening heart failure, death, or arrhythmias will be specifically 
documented as adverse events in the CRFs. 
A baseline sign and symptom is defined as an AE that starts after the patient has provided written 
informed consent and that resolves prior to the first dosing occasion, or an AE that starts prior to 
the first dosing occasion and does not increase in severity after dosing. A treatment-emergent AE 
(TEAE) is defined as an AE that occurs postdose or that is present predose and becomes more 
severe postdose.  
All AEs will be listed. The TEAEs will be summarized by treatment, severity, and relationship to 
the study drug. The frequency (the number of TEAEs, the number of patients experiencing a 
TEAE, and the percentage of patients experiencing a TEAE) of TEAEs and serious TEAEs will 
be summarized by treatment, and by MedDRA system organ class and preferred term. The 
summary and frequency TEAE tables will be presented for all causalities and for those TEAEs 
considered related to the study drug (those that have a relationship of probable or possible). A 
subset of serious adverse events and adverse events which are cardiac related, including the 
development of heart failure, will also be presented as summary tables. For any AEs that change 
severity ratings the AE will be included only once under the maximum severity rating in the 
summaries. Any life-threatening, severe or serious AEs will be listed. 
Onset times postdose are calculated from the start of study drug infusion. 
11.5.2 Clinical Laboratory Parameters 
Clinical chemistry (including thyroid function tests) and hematology data will be summarized by 
treatment group. Changes from baseline will be calculated. Shift tables from baseline will be 
presented. In addition, all clinical chemistry and hematology data outside the clinical reference 
ranges will be listed by parameter and treatment. 
Values for any clinical chemistry and hematology values outside the clinical reference ranges 
will be flagged on the individual patient data listings. 
11.5.3 Vital Signs 
Vital signs values outside the clinical reference ranges will be flagged on the individual patient 
data listings. 


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The vital signs data will be summarized by treatment group, together with changes from 
baseline.  Figures of mean vital signs and mean change from baseline profiles will be presented 
by treatment. Repeat and unscheduled readings will be handled as defined in Section 11.1.2.  
11.5.4 Incidence of Mortality 
The incidences of all-cause and cardiac mortality out to 6 months post PCI will be listed and 
tabulated by treatment group. 
11.5.5 Other Safety Assessments 
All other safety assessments not detailed in this section will be listed but not summarized or 
statistically analyzed. 
11.5.6 Safety and Tolerability Statistical Methodology 
No inferential statistical analyses are planned. 
11.6 
Pharmacokinetic Assessment 
11.6.1 Pharmacokinetic Analysis 
The following PK parameters will be determined where possible from plasma iodide 
concentrations using non-compartmental methods performed using Phoenix WinNonlin 
(Version 6.4 or higher): 


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Parameter 
Definition 
AUClast 
area under the concentration-time curve from time 0 to the time of the last 
observed quantifiable concentration (Tlast), calculated using the linear trapezoidal 
rule for increasing concentrations and the logarithmic rule for decreasing 
concentrations 
AUCinf 
area under the concentration-time curve extrapolated to infinity calculated using 
the following equation: 
AUCinf = AUClast + Ct/Kel 
where Ct is the last observed quantifiable concentration and Kel is the terminal 
elimination rate constant. 
Cmax 
maximal observed plasma concentration 
Tmax 
time when maximal concentration is achieved 
Tlast 
time of last quantifiable concentration 
Kel 
apparent terminal elimination rate constant 
T1/2 
apparent terminal elimination half-life, calculated as natural log (ln)(2)/Kel 
CL 
total body clearance  
Vz 
volume of distribution during the terminal elimination phase 
Vss 
volume of distribution at steady-state 
Additional PK parameters may be determined where appropriate. If the IV bolus model is used 
(refer to last bullet point in Section 11.6.4), then C0 (back-extrapolated concentration at time 
zero) may be calculated by excluding the observed predose concentration value and then using a 
log-linear regression of the first 2 postdose data points to back-extrapolate to the concentration at 
time 0. 
Pharmacokinetic analysis will, where possible, be carried out using actual postdose times 
recorded in the raw data. If actual times are missing, nominal times may be used with sponsor 
approval.  
Concentrations will be used as supplied by the analytical laboratory for PK analysis. The units of 
concentration and resulting PK parameters, with amount or concentration in the unit, will be 
presented as they are received from the analytical laboratory.  
The dose level of FDY-5301 (sodium iodide) will be converted to its free base equivalent for PK 
analysis if the analytical laboratory reports the free base concentration. 
Cmax, Tmax, and Tlast will be obtained directly from the plasma concentration-time profiles.   
For multiple peaks, the highest postdose concentration will be reported as Cmax. In the case that 
multiple peaks are of equal magnitude, the earliest Tmax will be reported. 


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11.6.2 Criteria for Handling Concentrations Below the Limit of Quantification in 
Pharmacokinetic Analysis 
 Concentration values that are below the limit of quantification (BLQ) will be set to zero, 
with defined exceptions as follows; 
o Any embedded BLQ value (between 2 quantifiable concentrations) and BLQ 
values following the last quantifiable concentration in a profile will be set to 
missing for the purposes of PK analysis. 
o If there are late positive concentration values following 2 BLQ concentration 
values in the apparent terminal phase, these values will be evaluated. If these 
values are considered to be anomalous, they will be set to missing. 
o If an entire concentration-time profile is BLQ, the profile will be excluded from 
the PK analysis. 
o If a predose concentration is missing, it may be set to zero with sponsor approval. 
11.6.3 Criteria for the Calculation of an Apparent Terminal Elimination Half-Life 
11.6.3.1 Number of Data Points 
 At least three data points will be included in the regression analysis and preferably should 
not include Cmax. 
11.6.3.2 Goodness of Fit 
 When assessing terminal elimination phases, the adjusted coefficient for the 
determination of exponential fit (R2 adjusted) will be used as a measure of the goodness 
of fit of the data points to the determined line.  
 Kel and Kel-based parameters will only be calculated if the R2 adjusted value of the 
regression line is greater than or equal to 0.7. 
11.6.3.3 Period of Estimation 
 Apparent terminal elimination half-life will be estimated over a time period of at least 
two half-lives, where possible.  
 Where T1/2 is estimated over a time period of less than two half-lives, it will be flagged in 
the data listings at the discretion of the Pharmacokineticist, and the robustness of the 
value should be discussed in the study report. 


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11.6.4 Calculation of AUC 
 The minimum requirement for the calculation of AUC will be the inclusion of at least 3 
consecutive plasma concentrations above the lower limit of quantification (LLOQ), with 
at least 1 of these concentrations following Cmax. 
 For any partial AUC determination, nominal time will generally be used for the end of the 
interval. Actual times for partial AUC intervals may be used at the discretion of the 
Pharmacokineticist.  
 AUCinf values where the percentage extrapolation is less than 20% will be reported. AUCinf 
values where the percentage extrapolation is between 20 to 30% will be reported, 
flagged, and included in the descriptive statistics, while AUCinf values where the 
percentage extrapolation is greater than 30% will be reported and flagged, but excluded 
from descriptive statistics.   
 If an IV bolus model is used, and if the combined area of back-extrapolated and infinity-
extrapolated is >30%, AUCinf may not be reported or a different model may be used 
(such as the infusion model), at the discretion of the Pharmacokineticist. 
11.6.5 Anomalous Values 
 If a value is considered to be anomalous due to being inconsistent with the expected PK 
profile, it may be appropriate to exclude this point from the PK analysis. However, the 
exclusion of data must have strong justification and will be documented in the raw data 
and study report. 
 Embedded BLQ values may be considered anomalous depending on the route of 
administration and the characteristics of the drug. 
11.6.6 Presentation of Pharmacokinetic Data 
11.6.6.1 Presentation of Pharmacokinetic Plasma Drug Concentration Data 
 The following rules will be applied if there are values that BLQ or if there are missing 
values (e.g., no result [NR]) in a plasma concentration data series to be summarized. 
o For the calculation of summary statistics, BLQ values will be set to zero. 
o If an embedded BLQ value is considered anomalous within the 
concentration-time profile, this value will be excluded from the summary 
statistics. 
o Where there is NR, these will be set to missing. 
o If there are less than 3 values in the data series, only the min, max and N will be 
presented.  The other summary statistics will be denoted as not calculated (NC).  
BLQ is considered a value. 


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o If all the values are BLQ, then the arithmetic mean, arithmetic SD, median, min 
and max will be presented as zero, and the geometric mean and geometric CV% 
will be denoted as NC. 
o If the value of the arithmetic mean or median is BLQ, it will be presented as zero, 
and the geometric mean and geometric CV% will be denoted as NC. 
11.6.6.2 Presentation of Pharmacokinetic Parameters 
 For the calculation of summary statistics of PK parameters, all NR and NC values in a data 
series will be set to missing. 
 The AUC values will be set to NC if they have been calculated using fewer than 
3 concentrations, and/or 3 concentrations if the last is Cmax. 
11.6.7 Pharmacokinetic Statistical Methodology 
All PK analyses will be performed with the PK population. 
All reportable plasma iodide concentration data and derived PK parameters will be summarized 
by treatment and listed. 
Plasma concentrations and derived PK parameters will be summarized in terms of N, arithmetic 
mean, SD, median, minimum, maximum, geometric mean and geometric CV%. For the PK 
parameter Tmax and Tlast, the descriptive statistics will not include geometric mean, and geometric 
CV%. Individual figures will also be presented using actual sampling times.  
There are no formal inferential statistical analyses planned. 
11.6.8 Pharmacokinetic/Efficacy Analysis 
A scatterplot will be produced to evaluate potential correlations between the Iodide plasma 
AUCinf and INF/VV at 3 months post-study drug. 
12  
INTERIM ANALYSES 
After the 14 day follow-up visit to the clinic, all patients’ data will be collected and analyzed for: 
 Safety (14-day arrhythmias) 
After the 3 month follow up visit, analysis of the following will occur: 
 Early efficacy outcomes including MSI, INF/VV, INF 
 Serum troponin AUC0-48 hours post-study drug 
 ST-segment resolution by 4 hours post-study drug 


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 Cardiac function including EDV, ESV, FS and EF 
All remaining assessments will be analyzed at the conclusion of the study. 
13  
CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES 
For the analysis of arrhythmias of interest, a person-time adjustment will be applied to account 
for potential missing data during the 14-day monitoring period, due to possible unforeseen 
reasons such as patient withdrawal, device failure or death. The incidence rate for each treatment 
group (and overall FDY-5301) will be calculated as the number of events divided by the total 
person-time of monitoring within each treatment group. The incidence rate ratios of each 
treatment group (and overall FDY-5301) versus the placebo will be derived.  
Scope of the interim analyses has been updated. 
Overall summary for primary and exploratory safety and efficacy endpoints will be summarized 
by stratification of TIMI flow grade and infarct location  
14  
DATA PRESENTATION 
14.1 
Insufficient Data for Presentation 
Some of the TFLs may not have sufficient numbers of patients or data for presentation. If this 
occurs, the blank TFL shell will be presented with a message printed in the center of the table, 
such as, “No serious adverse events occurred for this study.” 
15  
REFERENCES 
1. International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonized Tripartite Guideline, Statistical Principles 
for Clinical Trials (E9), 5 February 1998. 
2. International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonized Tripartite Guideline, Structure and 
Content of Clinical Study Reports (E3), 30 November 1995. 
 


12 April 2018