Clinical trial NCT04848220
Conditions: Microvascular Obstruction
Keywords: Temanogrel Microvascular obstruction APD791 Percutaneous coronary intervention MVO PCI
Sponsor: Pfizer
Start date: 2021-05-20; Completion date: 2022-08-31
Enrollment: 29 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine whether intravenous temanogrel is a safe and effective treatment for microvascular obstruction (MVO) in adult participants undergoing percutaneous coronary intervention (PCI).

Detailed description:
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to be conducted in 2 stages (Stage A and Stage B). Stage A is an ascending single-dose placebo-controlled study planned to consist of 2 cohorts. Stage B is a parallel-treatment group study planned to consist of a placebo group and 2 active treatment groups of temanogrel doses selected based on safety and tolerability data in Stage A.

Arms: arm 1: None arm 2: None arm 3: None
Interventions: intervention 1: Temanogrel intervention 2: Placebo
Intervention descriptions: intervention 1: Participants will receive a single intravenous dose of temanogrel on Day 1 (Day 1 of PCI procedure) intervention 2: Participants will receive a single intravenous dose of temanogrel matching placebo on Day 1

Protocol documents:
Prot_SAP_000.pdf: 
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Clinical Study Protocol 
 
APD791-202 
Temanogrel in PCI 
 
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PROTOCOL HISTORY  
Document 
Amendment Type 
Date 
Amendment 3.0 
Global 
17 May 2022 
Amendment 2.0 
Global 
15 March 2021 
Amendment 1.1 
Country-specific 
11 January 2021 
Amendment 1.0 
Global 
14 September 2020 
Original 0.0 
Global 
19 February 2020 


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PROTOCOL SYNOPSIS  
 
Sponsor: Arena Pharmaceuticals, Inc. 
Name of investigational study drug: Temanogrel (APD791) 
Protocol title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study 
to Assess the Safety, Tolerability, and Effect on Microvascular Obstruction of Temanogrel in 
Subjects Undergoing Percutaneous Coronary Intervention 
Protocol number: APD791-202 
Phase: 2 
Country(ies)/region(s) (planned): United States, Europe, and Australia 
Objectives: 
Primary: 
• To assess the effect of temanogrel on MVO following PCI 
Secondary: 
• To assess the effect of temanogrel on selected coronary physiology indices and 
angiographic measures following PCI 
• To assess the effect of temanogrel on myocardial injury following PCI 
• To assess the pharmacokinetics (PK) of temanogrel and its active metabolites 
AR295980 (M1) and AR295981 (M2) in subjects undergoing PCI 
• To assess the safety and tolerability of temanogrel in subjects undergoing PCI 
Study Design: 
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to be 
conducted in 2 stages (Stage A and Stage B). Each stage includes a Screening Period of up to 
14 days, a single dose of randomized study treatment (temanogrel or placebo) on Day 1 (day 
of PCI procedure), and a Follow-Up phone call 7 days (± 2 days) after administration of study 
treatment for a total study duration of 6 to 24 days. 
Upon confirmation of all inclusion/exclusion criteria, eligible subjects will be randomized on 
Day 1. Study treatment will be administered following assessment of Baseline angiographic 
measures, index of microcirculatory resistance (IMR) and additional coronary physiology 
indices, and blood sample collection (for assessment of peripheral serotonin concentration and 
additional laboratory assessments). Each subject will receive an intravenous (IV) single dose 
of study treatment. Assessment of IMR and additional coronary physiology indices will be 
repeated after administration of study treatment and before the start of the PCI procedure to 
obtain Pre-PCI values. Immediately after completion of PCI, the following assessments will be 
performed to obtain Post-PCI values: Assessment of IMR and additional coronary physiology 
indices, angiographic measures, and collection of blood samples (obtained from the coronary 
ostium and coronary artery distal to the lesion for assessment of coronary artery serotonin 


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concentration, as well as venous blood samples for peripheral serotonin concentration and 
additional laboratory assessments). 
Stage A is an ascending single-dose study planned to consist of 2 cohorts. After treatment of 
each cohort in Stage A, a safety/tolerability assessment will be conducted by the Data and 
Safety Monitoring Board (DSMB). Following the safety review of the first cohort in Stage A, 
the DSMB will recommend whether dose escalation to the next planned dose level in Stage A 
should occur; the DSMB may also recommend evaluation of an alternative dose in the second 
cohort in Stage A. Following the safety review of the second cohort in Stage A, the DSMB 
will recommend whether progression to Stage B should occur; the DSMB may also 
recommend evaluation of an alternative dose in an additional third dose cohort in Stage A 
prior to progression to Stage B. After conduct of the final cohort and safety review of Stage A, 
Stage B may begin. Stage B is a parallel-treatment group study planned to consist of a placebo 
group and 2 active treatment groups (temanogrel doses selected based on safety and 
tolerability data in Stage A). In Stage B, enrollment will consist of no more than 25% elective 
PCI subjects and randomization will be stratified subject type (elective PCI or PCI for 
non-ST-elevation myocardial infarction [NSTEMI]/unstable angina [UA]). 
Subjects should be treated with aspirin and an oral P2Y12 inhibitor (ie, dual antiplatelet 
therapy [DAPT]) per site standard of care; however, subjects in Stage A may only be treated 
with clopidogrel as the P2Y12 inhibitor DAPT component and may not be treated with 
prasugrel or ticagrelor until after the subject has completed study participation. 
Number of subjects (planned): 
Approximately 99 subjects are planned to be enrolled in this study. In Stage A, 2 cohorts are 
planned and approximately 6 subjects will be enrolled in each cohort (4 temanogrel:2 placebo 
per cohort). One additional cohort (4 temanogrel:2 placebo per cohort) may be enrolled to 
explore an additional dose if deemed appropriate based upon data reviews of prior cohorts. In 
Stage B, approximately 87 subjects are planned to be enrolled (29 subjects in each of the 
2 temanogrel treatment groups and the placebo group). 
Eligibility criteria: 
Inclusion criteria: 
Subjects must meet ALL of the following inclusion criteria to be eligible for enrollment into 
the study: 
1. Stable angina patients suitable for elective PCI or patients suitable for PCI for 
diagnosis of NSTEMI/UA. NSTEMI/UA patients are to be consistently 
hemodynamically stable until the time of PCI and have a thrombolysis in myocardial 
infarction (TIMI) Flow Grade () 2 or 3 on the diagnostic angiography. 
2. Target lesions for PCI must appear suitable for stenting as confirmed on the diagnostic 
angiography. Acceptable lesions cannot be in the left main artery or in a vein or arterial 
graft, or be a chronic total occlusion or in-stent restenosis. Two or more sequential 
lesions may be treated in the same artery, as long as they are treated in the same 
session and at least one of the lesions meets inclusion criteria.  


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• For elective PCI patients and non-urgent NSTEMI/UA patients (PCI >12 hours 
after diagnosis), the lesion must be located in a ≥ 2.75 mm diameter coronary 
artery; the lesion must also be ≥ 18 mm long and require the use of one or more 
stents that in total must be ≥ 20 mm long.  
• For NSTEMI patients treated with PCI urgently (within 12 hours after 
diagnosis), the coronary artery diameter of the culprit lesion must be 
≥ 2.75 mm. 
3. 30 to 80 years of age, inclusive 
4. Female subjects must not be lactating at the time of Screening 
5. Females must meet criterion a and males must meet criterion b to qualify for the study: 
a. Females must not be of childbearing potential by one of the following: 
• Postmenopausal, defined as no menses for 12 months without an alternative 
medical cause 
• Permanent sterilization procedure, such as hysterectomy, bilateral 
salpingectomy, or bilateral oophorectomy 
b. Males with pregnant or non-pregnant female partners of childbearing potential 
must agree to using a condom during treatment and for 90 days following treatment 
6. Body mass index 18.0 to 40.0 kg/m2, inclusive 
7. Willing to participate in the study and provide written informed consent 
Exclusion criteria: 
Subjects will be excluded from the study if they meet ANY of the following key exclusion 
criteria: 
1. Planned or anticipated use of rotational atherectomy/ablation or shockwave therapies 
during the PCI procedure 
2. Any history of stroke, seizure, intracranial bleeding, or intracranial aneurysm 
3. Transient ischemic attack within the 6 months prior to Screening 
4. History of major trauma, major surgery, and/or clinically significant head injury or 
hemorrhage within the last 6 months of Screening 
5. Any ST-elevation myocardial infarction (STEMI) within 10 days of Screening or 
STEMI within the target vessel territory within the last 4 months of Screening (eg, a 
patient with a NSTEMI because of a lesion in a diagonal may not be included if there 
is a history of anterior STEMI due to left anterior descending artery [LAD] lesion that 
occurred within the last 4 months) 
6. Known history of heart failure with reduced ejection fraction (HFrEF) defined as left 
ventricular ejection fraction ≤ 40% prior to current hospital admission 
7. Vasculitis within the last 6 months of Screening 
8. Known contraindication or allergy to heparin (eg, history of heparin-induced 
thrombocytopenia [HIT]), any antiplatelet agents (ie, aspirin, P2Y12 inhibitors), or 
adenosine 


Clinical Study Protocol 
 
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9. Use of any strong inhibitors or inducers of cytochrome P450 (CYP)3A4 or 
P-glycoprotein (examples include, but are not limited to, St. John’s wort, ketoconazole, 
itraconazole, clarithromycin, erythromycin, rifampicin, and verapamil) within 14 days 
or 5 half-lives (whichever is longer), relative to Check-in. Intra-arterial use of 
verapamil for subjects undergoing radial artery PCI is permitted 
10. Consumption of grapefruit within 3 days of Check-in 
11. Use of medications affecting the serotonin system (eg, selective serotonin reuptake 
inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], atypical 
[second generation] antipsychotics possessing 5-HT2A pharmacology, or any other 
serotonergic agents possessing 5-HT2A pharmacology [eg, the triazolopyridine 
antidepressant, trazodone]) within 14 days of Check-in 
12. Treatment with cangrelor or glycoprotein IIb/IIIa inhibitors within 24 hours of 
Check-in 
13. Need for chronic oral anticoagulant (eg, warfarin or direct oral anticoagulants 
[DOACs], including direct oral thrombin inhibitors) for any condition (eg, treatment of 
atrial fibrillation, deep vein thrombosis, or prosthetic cardiac valve) within 1 week of 
Check-in 
14. For subjects in Stage A ONLY: Use of prasugrel or ticagrelor within 14 days of 
Check-in 
Additional exclusion criteria are listed in Section 4.2. 
Test product, dose, and mode of administration: 
Temanogrel is an IV formulation containing active pharmaceutical ingredient provided as 
25 mg/mL strength. Temanogrel IV solution will be prepared by blinded study staff. Subjects 
assigned to active treatment will receive 1 single dose in total as a 5 mL IV bolus administered 
in the forearm over duration of at least 5 minutes. 
The temanogrel dose to be administered to Cohort 1 of Stage A will be 20 mg. The dose 
administered in Cohort 2 is planned to be 40 mg. One additional dose cohort may be explored 
in Stage A if deemed appropriate based upon data reviews of prior cohorts. Selected doses 
from Stage A are planned to be investigated in Stage B of the study. Planned doses in Stage A 
and Stage B may be adjusted depending on the safety and tolerability results of previous 
cohort(s). Doses in this study will not exceed 40 mg.  
Duration of treatment: 
Subjects will receive a single IV dose of study treatment on Day 1 of the study. 
Reference therapy, dose, and mode of administration: 
Placebo will be packaged to match temanogrel. Volume and mode of administration of 
placebo will match that of temanogrel to maintain the blind. 


Clinical Study Protocol 
 
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Amendment 3.0 
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Endpoints: 
Primary endpoint: 
• Change in IMR from Baseline to Post-PCI  
Secondary endpoints: 
• Change from Baseline to Post-PCI for the following assessments: 
o Coronary physiology indices (coronary flow reserve [CFR], fractional flow 
reserve [FFR]) 
o Angiographic measures (corrected thrombolysis in myocardial infarction frame 
count [cTFC], TFG, thrombolysis in myocardial infarction myocardial 
perfusion grade [TMPG]) 
o Myocardial injury markers (creatine kinase [CK], creatine kinase-myocardial 
band [CK-MB], cTn) 
Note: Post-PCI measure for CK, CK-MB, and cTn, is collected 4 to 6 hours after 
completion of the PCI procedure and not immediately after completion of the 
procedure. 
• The incidence of procedural myocardial injury defined as elevation of cTn values 
> 99th percentile upper reference limit (URL) in subjects with normal Baseline values 
(≤ 99th percentile URL) or elevation of cTn by > 20% of the Baseline value in subjects 
with elevated cTn levels (> 99th percentile URL) 
• Concentration of temanogrel and active metabolites AR295980 and AR295981 prior to 
PCI and at selected post-PCI timepoints until discharge 
• Safety and tolerability of temanogrel 
Pharmacokinetic assessments: 
Plasma concentrations of temanogrel (and its metabolites, AR295980 and AR295981) will be 
measured for each PK collection timepoint. Collected plasma PK samples may also be used 
for profiling of drug binding proteins, bioanalytical method validation purposes, stability 
assessments or to assess other actions of temanogrel (and/or its metabolites) with plasma 
constituents. 
Relationships between plasma concentration of selected analytes (temanogrel, its active 
metabolites, and/or all analytes combined) and selected PD measures (eg, change from 
Baseline to Post-PCI in IMR and other cardiac physiology indices, angiographic measures, 
markers of myocardial injury/infarction, or markers of inflammation) may be explored. 
Pharmacodynamic assessments 
Assessments of PD will include coronary physiology indices (IMR, coronary flow reserve 
[CFR], FFR), angiographic measures (cTFC, TFG, TMPG, QCA, assessment of lesion and 
vessel characteristics), markers of myocardial injury (CK, CK-MB, cTn), and markers of 
inflammation. 


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Amendment 3.0 
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Safety assessments: 
Safety assessments will include assessment of adverse events, vital signs, clinical laboratory 
tests, ECGs, and physical examinations. 
Statistical methods: 
Sample size: 
Approximately 99 subjects are planned to be enrolled in this study (12 in Stage A, 87 in 
Stage B). 
It is assumed that the primary endpoint, which is the change from Baseline in IMR measured 
immediately after PCI, is normally distributed with a mean of 6 and standard deviation (SD) of 
3.5. Assuming a 1:1:1 randomization, 90 evaluable subjects (30 subjects in each of the two 
temanogrel treatment groups and placebo) is sufficient to achieve at least 90% power to detect 
a treatment effect of 3 (a clinically significant reduction of 50% from placebo) between each 
of the temanogrel treatment groups and placebo by a 2-sample t-test using a 2-sided 
significance level of 0.05. 
The primary endpoint analysis will be based on pooled data from subjects in Stage A and 
Stage B. 
Stratification: 
Randomization in Part B will be stratified by subject type (elective PCI or PCI for 
NSTEMI/UA). 
Testing strategy: 
No formal testing strategy or adjustments of the Type I error will be employed for the 
evaluation of secondary or exploratory endpoints. Estimates and confidence intervals (CI) for 
treatment groups and from pairwise comparisons will be reported in an exploratory manner. 
Statistical analysis: 
The primary and secondary endpoints will be analyzed using the Full Analysis Set (FAS) and 
safety endpoints will be performed using the Safety Set. Other important statistical 
considerations, such as sensitivity analyses, and subgroup analyses will be described in the 
Statistical Analysis Plan (SAP). 
The primary endpoint of the study is the change from Baseline in IMR measured immediately 
after PCI. The primary PD analysis will be analyzed using analysis of covariance (ANCOVA) 
with a model that includes treatment group and randomization stratification factor as factors 
and Baseline IMR as a covariate. Least square means, standard errors (SEs), and 95% CIs for 
the treatments and their difference will be presented together with their p-values. 
Unless otherwise specified, secondary continuous endpoints will be analyzed using ANCOVA 
with a model that includes treatment group and randomization stratification factor as factors 
and Baseline IMR value and Baseline values as covariates. Least square means, SEs, and 95% 
CIs for the treatments and their difference will be presented together with their p-values. 
Proportion-based secondary endpoints will be analyzed in the FAS using the 
Cochran-Mantel-Haenszel method adjusted for randomization stratification factor. The 
number and percentage of subjects achieving the goal and the difference in proportion 
between treatment groups achieving the goal, along with p-value and the 95% CIs will be 


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reported. The odds ratio relative to placebo and percentage of difference from placebo will be 
presented together with corresponding 95% CIs and the p-values. 
Pairwise comparisons of each temanogrel treatment group compared to placebo will be 
conducted. In addition, analyses of the pooled temanogrel treatment groups compared to 
placebo will be conducted. 
Where statistical assumptions (eg, normality, proportional odds) are not met, alternative 
approaches will be evaluated (eg, non-parametric analysis, log transformation). 
Details regarding the statistical analyses will be provided in the SAP. 
Pharmacokinetic analysis: 
The PK analysis will be conducted using model independent methods and based on plasma 
concentrations of temanogrel and its metabolites from subjects who have received temanogrel 
and have evaluable plasma concentration versus time profiles. The Pharmacokinetic Set will 
be used to analyze plasma concentrations. Detailed PK analysis procedures will be provided in 
the SAP. 
Safety analysis: 
Adverse Event will be listed and summarized by system organ class and preferred term, as 
well as according to severity and causality/relationship to temanogrel. Treatment-emergent 
adverse events (TEAEs) will be summarized by stage, cohort, and treatment group. In 
addition, TEAEs will be pooled across treatment groups (ie, placebo, temanogrel). Similarly, 
bleeding events will be summarized by Bleeding Academic Research Consortium (BARC) 
classification by stage, cohort, and treatment group and pooled across treatment groups. 
Observed values for clinical laboratory tests, vital signs, and safety 12-lead ECGs, will be 
summarized by stage, cohort, treatment group, and timepoint. Individual data listings of 
clinical laboratory tests results will be presented for each subject. Observed values and 
changes from Baseline will be summarized descriptively. Safety 12-lead ECG data (observed 
values and change from Baseline) will be listed for each subject and timepoint. Observed 
values will be classified for normal, abnormality that is not clinically significant, and clinically 
significant abnormality by stage, cohort, treatment, and timepoint of collection. Results of 
other safety assessments will be listed and summarized as appropriate. 
Interim analysis: 
No formal interim analysis of efficacy is planned.  
 


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TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL ..................................................................................................1 
PROTOCOL HISTORY ..................................................................................................................2 
PROTOCOL SYNOPSIS ................................................................................................................3 
LIST OF APPENDICES ................................................................................................................14 
LIST OF TABLES .........................................................................................................................14 
LIST OF FIGURES .......................................................................................................................14 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................15 
1. 
INTRODUCTION ......................................................................................................19 
1.1. 
Background .................................................................................................................20 
1.1.1. 
Clinical Experience .....................................................................................................21 
1.2. 
Benefit-Risk Considerations .......................................................................................21 
2. 
OBJECTIVES .............................................................................................................23 
3. 
STUDY DESIGN .......................................................................................................24 
3.1. 
Overall Design ............................................................................................................24 
3.2. 
Scientific Rationale for Study Design ........................................................................27 
3.3. 
Rationale for Dose Selection ......................................................................................28 
4. 
STUDY POPULATION .............................................................................................29 
4.1. 
Inclusion Criteria ........................................................................................................29 
4.2. 
Exclusion Criteria .......................................................................................................29 
5. 
SUBJECT RESTRICTIONS ......................................................................................32 
5.1. 
Restricted Medications ...............................................................................................32 
5.2. 
Dietary Restrictions ....................................................................................................32 
6. 
STUDY TREATMENT ..............................................................................................33 
6.1. 
Study Treatment(s) Administered ...............................................................................33 
6.2. 
Identity of Study Treatments ......................................................................................33 
6.2.1. 
Temanogrel .................................................................................................................33 
6.2.2. 
Placebo ........................................................................................................................33 
6.3. 
Dosage and Administration ........................................................................................34 
6.3.1. 
Instructions for Missed Dose(s) ..................................................................................34 
6.3.2. 
Dose Interruptions ......................................................................................................34 
6.4. 
Method of Assigning Subjects to Treatment ..............................................................34 


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6.5. 
Blinding ......................................................................................................................35 
6.6. 
Treatment Compliance ................................................................................................35 
6.7. 
Concomitant Therapy .................................................................................................35 
6.7.1. 
Required Concomitant Therapy ..................................................................................36 
6.7.2. 
Allowed Concomitant Therapy ...................................................................................36 
7. 
STUDY TREATMENT AND MATERIALS MANAGEMENT ..............................37 
7.1. 
Packaging and Labeling ..............................................................................................37 
7.2. 
Storage and Handling .................................................................................................37 
7.3. 
Preparation ..................................................................................................................37 
7.4. 
Study Drug Accountability .........................................................................................37 
7.5. 
Study Treatment Retention and Disposal ...................................................................38 
8. 
REMOVAL OF SUBJECTS FROM THERAPY OR ASSESSMENT .....................39 
8.1. 
Discontinuation of Study Treatment ...........................................................................39 
8.2. 
Discontinuation from the Study ..................................................................................39 
8.3. 
Lost to Follow-Up.......................................................................................................39 
8.4. 
Premature Termination of the Study or Study Site .....................................................40 
9. 
STUDY PERIODS .....................................................................................................41 
9.1. 
Screening and Enrollment ...........................................................................................41 
9.2. 
Treatment Period ........................................................................................................41 
9.3. 
Follow-Up Phone Call/End of Study ..........................................................................41 
9.4. 
Early Termination .......................................................................................................42 
10. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................43 
10.1. 
Subject Informed Consent ..........................................................................................43 
10.2. 
Screening and Eligibility ............................................................................................43 
10.2.1. 
Rescreening .................................................................................................................43 
10.2.2. 
Demography and Other Subject Characteristics .........................................................43 
10.2.3. 
Prior and Ongoing Therapies ......................................................................................43 
10.2.4. 
Medical History ..........................................................................................................43 
10.2.5. 
Clinical Chemistry and Hematology ..........................................................................44 
10.2.6. 
Diagnostic Angiography .............................................................................................44 
10.3. 
Percutaneous Coronary Intervention ..........................................................................44 
10.4. 
Pharmacodynamic Assessments .................................................................................44 
10.4.1. 
Coronary Physiology Indices ......................................................................................44 


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10.4.1.1. 
Index of Microcirculatory Resistance .........................................................................45 
10.4.1.2. 
Coronary Flow Reserve ..............................................................................................45 
10.4.1.3. 
Fractional Flow Reserve .............................................................................................45 
10.4.2. 
Angiographic Measures ..............................................................................................45 
10.4.2.1. 
TIMI Flow Grade ........................................................................................................46 
10.4.2.2. 
Corrected TIMI Frame Count .....................................................................................46 
10.4.2.3. 
TIMI Myocardial Perfusion Grade .............................................................................46 
10.4.2.4. 
Quantitative Coronary Analysis .................................................................................46 
10.4.3. 
Markers of Myocardial Injury ....................................................................................46 
10.4.3.1. 
Creatine Kinase ...........................................................................................................46 
10.4.3.2. 
Creatine Kinase-Myocardial Band .............................................................................46 
10.4.3.3. 
Cardiac Troponin ........................................................................................................47 
10.4.4. 
Markers of Inflammation ............................................................................................47 
10.5. 
Pharmacokinetic Assessments ....................................................................................47 
10.6. 
Serotonin .....................................................................................................................47 
10.6.1. 
Peripheral Serotonin ...................................................................................................47 
10.6.2. 
Coronary Artery Serotonin .........................................................................................48 
10.6.3. 
Future Biomarker Research ........................................................................................48 
10.7. 
P2Y12 VerifyNow Assay .............................................................................................48 
10.8. 
Safety Assessments .....................................................................................................48 
10.8.1. 
Vital Signs ..................................................................................................................48 
10.8.2. 
Physical Examinations ................................................................................................49 
10.8.3. 
Electrocardiography ....................................................................................................49 
10.8.4. 
Clinical Laboratory Assessments ...............................................................................49 
10.8.4.1. 
Clinical Chemistry, Hematology, and Coagulation ....................................................52 
10.8.4.2. 
Drugs of Abuse ...........................................................................................................52 
10.8.5. 
Adverse Events ...........................................................................................................52 
10.8.5.1. 
Definitions ..................................................................................................................52 
10.8.5.2. 
Eliciting, Recording, and Reporting Adverse Events .................................................55 
10.8.5.3. 
Reporting Serious Adverse Events .............................................................................56 
10.8.5.4. 
BARC Bleeding Criteria Assessment .........................................................................57 
10.8.6. 
Pregnancy ...................................................................................................................58 
10.9. 
Order of Events and Priority for Timed Assessments ................................................58 


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10.10. 
Safety-Related Stopping Criteria ................................................................................59 
10.11. 
DSMB Review: Safety-Related Dose Escalation (Stage A)/Dose 
Recommendation (Stage B) Criteria ...........................................................................59 
10.12. 
Approximate Blood Volume .......................................................................................59 
10.13. 
Procedures for Overdose .............................................................................................59 
11. 
PLANNED STATISTICAL METHODS ...................................................................61 
11.1. 
General Considerations ...............................................................................................61 
11.2. 
Determination of Sample Size ....................................................................................61 
11.3. 
Analysis Sets ...............................................................................................................62 
11.4. 
Missing Data ...............................................................................................................62 
11.5. 
Efficacy Analyses .......................................................................................................62 
11.6. 
Study Endpoints ..........................................................................................................62 
11.6.1. 
Primary Endpoint ........................................................................................................62 
11.6.2. 
Secondary Endpoints ..................................................................................................62 
11.6.3. 
Exploratory Endpoints ................................................................................................63 
11.6.4. 
Pharmacokinetic Analysis ..........................................................................................63 
11.6.5. 
Pharmacokinetic/Pharmacodynamic Relationship .....................................................64 
11.7. 
Subgroup Analysis ......................................................................................................64 
11.8. 
Testing Strategy ..........................................................................................................64 
11.9. 
Interim Analysis ..........................................................................................................64 
11.10. 
Safety Analyses ..........................................................................................................64 
11.10.1. 
Safety Endpoints .........................................................................................................65 
11.10.2. 
Adverse Events ...........................................................................................................65 
11.10.3. 
Clinical Laboratory Parameters ..................................................................................66 
11.10.4. 
Electrocardiograms .....................................................................................................66 
11.10.5. 
Vital Signs ..................................................................................................................66 
11.10.6. 
Physical Examination .................................................................................................66 
11.11. 
Data and Safety Monitoring Board .............................................................................66 
12. 
ETHICAL CONSIDERATIONS................................................................................68 
12.1. 
Ethical Conduct of the Study ......................................................................................68 
12.2. 
Institutional Review Board or Independent Ethics Committee Approval ..................68 
12.3. 
Informed Consent .......................................................................................................68 
12.4. 
Confidentiality ............................................................................................................69 


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12.5. 
Protocol Compliance ..................................................................................................69 
13. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................70 
13.1. 
Training of Study Site Personnel ................................................................................70 
13.2. 
Monitoring ..................................................................................................................70 
13.3. 
Audit ...........................................................................................................................70 
14. 
DATA HANDLING AND RECORD KEEPING ......................................................71 
14.1. 
Data Management .......................................................................................................71 
14.1.1. 
Case Report Forms .....................................................................................................71 
14.1.2. 
Source Documents ......................................................................................................71 
14.2. 
Study Documentation and Records Retention ............................................................71 
14.3. 
Clinical Study Report .................................................................................................72 
14.4. 
Disclosure of Study Results ........................................................................................72 
15. 
RESPONSIBILITIES .................................................................................................73 
15.1. 
Investigator Responsibilities .......................................................................................73 
15.2. 
Sponsor Responsibilities .............................................................................................73 
16. 
REFERENCES ...........................................................................................................74 
 
LIST OF APPENDICES  
APPENDIX 1: SCHEDULE OF ASSESSMENTS ....................................................................79 
APPENDIX 2: INVESTIGATOR SIGNATURE .......................................................................83 
 
LIST OF TABLES  
Table 1: 
Study Treatments ........................................................................................................33 
Table 2: 
Clinical Laboratory Tests ...........................................................................................51 
Table 3: 
BARC Definitions for Bleeding .................................................................................57 
Table 4: 
Analysis Sets ...............................................................................................................62 
 
LIST OF FIGURES  
Figure 1: 
Schematic Diagram of Study Design ..........................................................................25 
Figure 2: 
Subject Flow of Events ...............................................................................................26 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS  
Abbreviation 
Explanation 
5-HT 
serotonin 
ACC 
American College of Cardiology 
ACS 
acute coronary syndrome 
ADP 
adenosine diphosphate 
ADR 
adverse drug reaction 
AHA 
American Heart Association 
ALP 
alkaline phosphate 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
APD791 
temanogrel 
aPTT 
activated partial thromboplastin time 
Arena 
Arena Pharmaceuticals, Inc. 
AST 
aspartate aminotransferase 
AUC0-∞ 
area under the single-dose plasma or serum concentration-time curve extrapolated to 
infinity 
AUC0-t 
area under the plasma concentration vs. time curve from time zero to the time of the 
last quantifiable plasma sample 
BARC 
Bleeding Academic Research Consortium 
BUN 
blood urea nitrogen 
CABG 
coronary artery bypass graft 
CAD 
coronary artery disease 
CFR 
coronary flow reserve 
CI 
confidence interval 
CK 
creatine kinase 
CKD-Epi 
Chronic Kidney Disease Epidemiology Collaboration 
CK-MB 
creatine kinase-myocardial band 
Cmax 
observed maximum plasma concentration 
CMP 
Clinical Monitoring Plan 
CMR 
cardiac magnetic resonance 
CRO 
Contract Research Organization 
cTFC 
corrected thrombolysis in myocardial infarction frame count 
cTn 
cardiac troponin 
cTnI 
cardiac troponin I 
CVD 
cardiovascular disease 


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Abbreviation 
Explanation 
CYP 
cytochrome P450 
DAPT 
dual antiplatelet therapy 
DNA 
deoxyribonucleic acid 
DOAC 
direct oral anticoagulants 
DSMB 
Data and Safety Monitoring Board 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
ESC 
European Society of Cardiology 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FFR 
fractional flow reserve 
GCP 
Good Clinical Practice 
HIT 
heparin-induced thrombocytopenia 
HIV 
human immunodeficiency virus 
HR 
heart rate 
hs-CRP 
highly sensitive C-reactive protein 
hs-cTnT 
high-sensitive cardiac troponin T 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IL 
interleukin 
IMR 
index of microcirculatory resistance 
IMRcorr 
IMR corrected for the influence from collateral supply 
IND 
Investigational New Drug 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IRT 
interactive response technology 
IV 
intravenous 
Ki 
inhibition constant 
LAD 
left anterior descending artery 
LDH 
lactate dehydrogenase 
M1 
AR295980 


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Abbreviation 
Explanation 
M2 
AR295981 
MBG 
myocardial blush grade 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
mFAS 
modified Full Analysis Set 
MI 
myocardial infarction 
MVO 
microvascular obstruction 
NSTEMI 
non-ST-elevation myocardial infarction 
Pa 
mean aortic pressure at max hyperemia 
PCI 
percutaneous coronary intervention 
PD 
pharmacodynamic 
Pd 
mean distal coronary pressure at max hyperemia 
PK 
pharmacokinetic 
PRP 
platelet-rich plasma 
PT 
prothrombin time 
PTX-3 
Pentraxin-3 
Pw 
coronary wedge pressure 
q8h 
every 8 hours 
QCA 
quantitative coronary analysis 
QTcB 
corrected QT interval using Bazett’s formula 
QTcF 
corrected QT interval using Fridericia’s formula 
RBC 
red blood cell 
RNA 
ribonucleic acid 
RSI 
reference safety information 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
standard deviation 
SE 
standard error 
SNRI 
serotonin-norepinephrine reuptake inhibitor 
SOP 
standard operating procedure 
SSRI 
selective serotonin reuptake inhibitor 
STEMI 
ST-elevation myocardial infarction 


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Abbreviation 
Explanation 
t½ 
apparent terminal elimination half-life 
TEAE 
treatment emergent adverse event 
TFG 
thrombolysis in myocardial infarction flow grade 
TIMI 
thrombolysis in myocardial infarction 
tmax 
observed time of Cmax 
TMF 
trial master file 
Tmn 
mean transit time at maximal hyperemia 
TMPG 
TIMI myocardial perfusion grade 
TNF-α 
tumor necrosis factor alpha 
TSH 
thyroid-stimulating hormone 
UA 
unstable angina 
ULN 
upper limit of normal 
URL 
upper reference limit 
US 
United States 
Vd 
volume of distribution 
WBC 
white blood cell 
WHF 
World Heart Federation 
 


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1. 
INTRODUCTION  
Cardiovascular disease (CVD), is the leading cause of death globally (WHO 2017). Among 
CVD, coronary artery disease (CAD) is the single most common cause of death, resulting in 1 in 
every 4 deaths in the US (CDC 2017). The main cause of CAD is atherosclerosis, an 
inflammatory disease characterized by focal thickenings of the arterial intima containing lipids, 
connective tissue, and various cell types. Atherosclerotic plaque build-up progressively narrows 
the lumen of coronary arteries and leads to clinical symptoms such as angina. Highly 
inflammatory and unstable plaques (vulnerable plaques) may eventually rupture and lead to 
potentially fatal events such as myocardial infarction (MI) (Hansson 2011). In both cases, the 
prevention of oxygen delivery to the myocardium through impaired or blocked coronary blood 
flow gives rise to clinical events. 
Significant advances have been made in medical therapy to prevent or treat CAD; however, since 
the disease is often detected in a late stage and difficult to reverse, a large percentage of patients 
remain symptomatic or develop complications and require invasive, mechanical interventions 
such as percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) (Kolh 
2014, Neumann 2019). Despite broad implementation of primary PCI and an improvement in 
“door-to-balloon” times, corresponding improvement in mortality has plateaued in recent years 
(Menees 2013). Notably, a significant proportion of patients undergoing PCI, mainly for 
treatment of acute coronary syndrome (ACS), fail to achieve full myocardial or microcirculatory 
reperfusion despite resolution of the epicardial coronary occlusion (Bouleti 2015, Rezkalla 
2017). This is sometimes expressed angiographically as slow/no-reflow, but even in cases with 
normal epicardial flow, microvascular obstruction (MVO) can detrimentally affect 
microcirculatory perfusion and has been reported in approximately 40-60% of patients 
undergoing PCI for ST-elevation myocardial infarction (STEMI) and in up to 30% of cases in 
the non-STEMI (NSTEMI) population (higher in severe NSTEMI cases) (Carrick 2016, Cuculi 
2014, de Waha 2017, Durante 2017, Guerra 2014, McGeoch 2010, Niccoli 2016, Van Assche 
2011, van Kranenburg 2014). Importantly, the presence of MVO post-PCI has been associated 
with worse clinical outcomes including mortality and hospitalization for heart failure, related to 
suboptimal cardiac function and recovery in the days and months following the PCI procedure 
(Carrick 2016, de Waha 2017, Fearon 2013, McGeoch 2010, Niccoli 2016, Nijveldt 2008, Orn 
2009). Several treatment options have been explored including the use of vasodilators and 
antiplatelet agents; however, clinical efficacy data from these interventions is limited and 
currently no treatment has been demonstrated to be beneficial for prevention or treatment of 
MVO following PCI (Jaffe 2010, Niccoli 2016, Rezkalla 2017, Salinas 2012). Therefore, there is 
an unmet need for safe and effective agents to prevent and treat MVO in the PCI setting, 
resulting in improved cardiac functional recovery and clinical outcomes. 
In patients with CAD/ACS, particularly those with complex lesion morphology, levels of 
serotonin (5-HT) are elevated and associated with cardiac events (Rouzaud Laborde 2013, van 
den Berg 1989, Vikenes 1999). During angioplasty or PCI, levels of 5-HT may be further 
increased when platelets become activated following rupture of the atherosclerotic plaque, which 
can be either procedure-induced or occur spontaneously (Adlbrecht 2007, Golino 1994, 
Kleinbongard 2013, Kleinbongard 2011, Leosco 1999). Upon activation, platelets release 5-HT 
in substantial quantities causing amplification of platelet aggregation, vasoconstriction, and 
cardiac remodeling (Mc Fadden 1993, Rouzaud-Laborde 2015). Specifically, 5-HT acts on 


Cli nical St u d y Pr ot oc ol  
 
A P D 7 9 1 -2 0 2  
T e ma n o grel i n P CI  
 
A me n d me nt 3. 0  
Are na P har mace uticals, I nc.  
C o nfi de ntial  
P a ge 2 0  of 8 3  
5 -H T 2 A rece pt ors o n t he s urface of platel ets t o a m plif y a g gre gati o n i n d uce d b y ot her fact ors s uc h 
as a de n os i ne di p h os p hate ( A D P), c olla ge n, or da m a ge d e n d ot heli u m (De Clerc k 1 9 8 3 , De Clerc k 
1 9 9 0 ) a n d acts as a p ote nt sti m ulat or of vas oc o nstricti o n b y acti vati n g 5 -H T 2 A rece pt ors o n 
s m o ot h m uscle cells (Wri g ht 1 9 9 2 ). 5-H T release fr o m acti vate d plat elets h as bee n i m plicate d i n 
me diati n g a n e x a g gerate d platelet res p o nse i n pati e nts wit h A C S (S hi m b o 2 0 0 2 ), res ulti n g i n 
platelet a g gre gati o n a n d t hr o m b us f or mati o n (Be n e dict 1 9 8 6 , Li 1 9 9 7 ). A d diti o nall y, release of 
5 -H T i n t he c or o nar y cir c ulati o n d uri n g a n gi o plast y or P CI is ass ociat e d wit h vas oc o nstricti o n 
distal t o t he lesi o n site, a n d t his effect c o ul d b e att e n uate d wit h 5 -H T 2 A a nt a g o nis m (G oli n o 
1 9 9 4 , Klei n b o n gar d 2 0 1 1 , Le os c o 1 9 9 9 ). T h us, 5-H T is ele vate d i n t he P CI s etti n g a n d is 
i m plicate d i n pat h ol o gical mec ha nis ms ass ociate d wit h de vel o p me nt of M V O (e g, 
vas oc o nstricti o n, platelet acti vati o n), w hic h ma y c o ntri b ute t o sl o w/ n o refl o w a n d m ore se v ere 
m y ocar dial da ma ge (Carric k 2 0 1 6 , De Mari a 2 0 1 9 , Nicc oli 2 0 0 9 , P a y n e 2 0 1 2 ). Bas e d o n 
e vi de nce s u g gesti n g a n i m p orta nt r ole of 5 -H T i n a m plificati o n of plate let a g gre gati o n a n d 
vas oc o nstricti o n wit hi n t he micr ocir c ulati o n at t he ti me of P CI, bl oc ki n g t he 5 -H T -me di ate d 
effects i n t his setti n g is a ntici pate d t o pre ve nt or mi ni mize t he de vel o p me nt of M V O.  
St u d y  A P D 7 9 1 -2 0 2 is a m ultice nter, ra n d o mize d, bli n de d, pl ace b o-c o ntr olle d, P hase  2 st u d y t o  
assess t he safet y, t olera bilit y, p h ar mac o ki netic ( P K), a n d p har mac o d y n a mic ( P D) of i ntra v e n o us 
(I V) te ma n o grel after a d mi nistrati o n of si n gle d oses t o s u bjects u n der g oi n g P CI. T he st u d y will 
be c o n d ucte d i n c o m plia nce wit h I C H g ui deli nes f or G C P a n d a p plica ble re g ul at or y 
re q uire me nts, t he st u d y pr ot oc ol, a n d w here a p plica ble, S p o ns or a n d/ or C o ntract Researc h 
Or ga niz ati o n ( C R O) sta n dar d o perati n g pr oce d ures ( S O Ps).  
1. 1.  
B a c k gr o u n d   
Te ma n o grel ( A P D 7 9 1) is a c he mical e ntit y bei n g de vel o pe d b y Are na  P har mace uticals, I n c. 
( Are n a) f or t he treat me nt of M V O . As a p ote nt i n verse a g o nist of t he 5-H T 2 A rece pt or, 
te ma n o grel i n hi bits 5-H T -me diate d a m plificati o n of platelet a g gre gati o n a n d bl oc ks 
5 -H T -me diate d v as oc o nstricti o n t hr o u g h its acti o n at 5 -H T 2 A rece pt ors o n t he s urface of pl atelets 
a n d s m o ot h m uscle cells, res pecti vel y. 
 
 
 
 
St u dies usi n g ra b bit a orta s h o we d t hat te ma n o grel bl oc ke d 5 -H T -i n duce d v as oc o nstricti o n, a n d 
d ose de pe n de ntl y i n hi bite d 5 -H T -sti m ulate d pr oliferati o n of ra b bit a ortic s m o ot h m uscle cells 
(A da ms 2 0 0 7 , A da ms 2 0 0 9 ). F urt her m ore, te m a n o grel i n hi bite d 5-H T -me diate d a m plificati o n of 
i n vitr o A D P -i n d uce d platelet a g gre gati o n i n h u ma n, m o n ke y, a n d ca ni n e platelet-ric h plas m a 
( P R P) i n a d ose-de pe n d e nt ma n ner. Oral a d mi nistrati o n of te ma n o grel t o ca ni nes  was hi g hl y 
effecti ve at i n hi biti n g 5 -H T -me diate d a m plificati o n of c olla ge n -i n d u ce d platelet a g gre gati o n 
e x  vi v o at 1  h o ur after st u d y treat me nt a d mi nistrati o n. I n t he ca ni ne F olts m o del of c or o nar y 
arter y o ccl usi o n (Prz y kle n k 2 0 1 0 ), I V te ma n o grel i nf usi o n o ver a 3-h o ur peri o d was ass ociat e d 
wit h i ncrease d fl o w -ti me area a n d re d uce d d urati o n of zer o fl o w o ver t h e sa me ti me peri o d 
c o m pare d t o place b o.  T h ese i m pr o ve me nts were n ot acc o m pa nie d b y a n y i ncreas e i n blee di n g.  
A c o m plete s u m mar y of t he n o ncli nical data rele va nt t o t he i n vesti gati o nal pr o d uct a n d its st u d y  
i n h u ma n s u bjects is pr o vi de d i n t he c urre nt e diti o n of t he I n vesti gat or’s Br oc h ure (I B). 
C CI


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1.1.1. 
Clinical Experience  
The safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) of orally 
administered temanogrel and its primary metabolites AR295980 and AR295981 have been 
evaluated in 4 completed Phase 1 studies in healthy adult human subjects, 2 in the US and 2 in 
South Korea. The US studies evaluated safety, tolerability, PK, and PD effects of single and 
repeated doses of oral temanogrel. The 2 studies conducted in South Korea evaluated safety, 
tolerability, PK, and PD effects of single and repeated doses of temanogrel alone and 
co-administered with aspirin and clopidogrel (dual antiplatelet therapy [DAPT]). 
Intravenously administered temanogrel has been evaluated in 1 Phase 1 clinical study in healthy 
adult human subjects. The study evaluated safety, tolerability, PK, and PD of temanogrel and its 
primary metabolites AR295980 and AR295981 after administration of single IV doses. 
A complete summary of the clinical data relevant to the investigational product and its study in 
human subjects is provided in the current edition of the IB. 
1.2. 
Benefit-Risk Considerations  
As of the date of this protocol, the safety, tolerability, PK, and PD of temanogrel have been 
assessed in 5 Phase 1 studies in healthy subjects. Single and repeated doses of oral temanogrel 
were evaluated in 4 studies, and single IV doses of temanogrel were evaluated in a separate 
study. In completed clinical studies, doses of temanogrel planned to be used in this study were 
well-tolerated and there were no associated safety concerns. The most common adverse events in 
subjects treated with single doses of IV temanogrel were mild pain and redness at the treatment 
administration site. In healthy volunteers who received single oral doses of temanogrel, the most 
common side effects were dizziness and headache, and less commonly tiredness, back pain, skin 
rash, and nausea. 
Although the incidence and severity of MVO in the PCI setting with the chosen study population 
(elective PCI or PCI for NSTEMU/UA) is reduced compared to primary PCI for STEMI, MVO 
remains a problem in the chosen study population as impaired microcirculation is often observed 
in this setting as well. In all patients undergoing PCI, temanogrel is expected to exert antiplatelet 
and anti-vasoconstrictive effects and improve microvascular coronary perfusion. 
Antiplatelet agents, such as temanogrel, can be associated with increased bleeding risk 
(Wallentin 2009, Wiviott 2007, Yusuf 2001). Platelet aggregation is primarily triggered by 
factors such as ADP, thrombin, collagen, or damaged endothelium (Saini 2004, Vikenes 1999), 
while 5-HT mediates amplification of platelet aggregation induced by these factors via activation 
the 5-HT2A receptors present on the surface of platelets. Targeting the 5-HT pathway with 
temanogrel is predicted to exert the greatest antiplatelet effect at sites of vascular injury where 
5-HT levels are high. Hence, bleeding risk may be greatest during invasive procedures, injuries, 
or pathological processes that affect the integrity of vascular endothelium. However, considering 
that temanogrel does not inhibit primary platelet aggregation pathways but instead attenuates the 
amplification of platelet aggregation mediated by 5-HT, the associated bleeding risk is expected 
to be significantly lower compared to standard antiplatelet agents. Completed clinical studies 
include the assessment of IV temanogrel alone and oral temanogrel administered alone or 
co-administered with dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel. 
Bleeding-related side effects seen in healthy subjects who received single doses of IV 


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temanogrel alone up to 40 mg were mild bruising at the site of blood vessel puncture, and 2 of 
the 47 participants (including a participant treated with placebo) experienced nosebleed. When 
oral temanogrel was given to healthy subjects as single dose alone (up to 320 mg), there were no 
observed bleeding events. Two cases of nosebleed occurred with the highest evaluated dose of 
oral temanogrel alone (total daily dose 240 mg) following multiple days of dosing. In the studies 
where single doses of oral temanogrel were co-administered with DAPT, there was an increase 
in mild bleeding-related events (primarily bruising at the site of blood draw and red spots on the 
skin). Mild bleeding events were also observed with lower multiple doses of oral temanogrel 
co-administered with DAPT; however, the bleeding risk was generally similar in the placebo and 
temanogrel treatment groups.  
Convulsions were noted in rats following a single IV (bolus) at ≥ 60 mg/kg temanogrel, and 
generalized seizures in monkeys at oral doses ≥ 100 mg/kg/day temanogrel. The 
no-observed-adverse-effect levels (NOAELs) in these studies were 20 mg/kg (acute IV rat study) 
and 35 mg/kg/day (oral 4-week monkey study). Similar nervous system-related findings have not 
been observed with temanogrel administration to healthy subjects at exposure margins of at least 
2.3-fold following a single 320 mg oral dose (based on the lowest Cmax at the oral 4-week 
monkey study NOAEL) and 7.3-fold following a single 40 mg IV dose (based on the lowest Cmax 
at the acute IV rat study NOAEL). 
Additional risks of participation in the study are primarily those associated with adverse 
reactions to the study treatments, although there may also be some discomfort from collection of 
blood samples and other study procedures. Further description of identified risks, any potential 
risks, and the reference safety information for temanogrel are provided in the current edition of 
the IB. 


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2. 
OBJECTIVES  
Primary Objective 
• To assess the effect of temanogrel on MVO following PCI 
Secondary Objectives 
• To assess the effect of temanogrel on selected coronary physiology indices and 
angiographic measures following PCI 
• To assess the effect of temanogrel on myocardial injury following PCI 
• To assess the PK of temanogrel and its active metabolites AR295980 (M1) and 
AR295981 (M2) in subjects undergoing PCI 
• To assess the safety and tolerability of temanogrel in subjects undergoing PCI 
Exploratory Objectives 
• To assess selected exposure-response (PK/PD) relationships 
• To assess the relationship between selected coronary physiology indices/angiographic 
measures and serotonin concentrations 
• To assess the relationship between the level of P2Y12 platelet inhibition and serotonin 
concentrations 
• To assess the effect of temanogrel on: 
o Selected coronary physiology indices prior to PCI  
o Selected angiographic measures following PCI 
o Post-procedural markers of inflammation 


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3. 
STUDY DESIGN  
3.1. 
Overall Design  
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to be 
conducted in 2 stages (Stage A and Stage B) (Figure 1). Each stage includes a Screening Period 
of up to 14 days, a single dose of randomized study treatment (temanogrel or placebo) on Day 1 
(day of PCI procedure), and a Follow-Up phone call 7 days (± 2 days) after administration of 
study treatment for a total study duration of 6 to 24 days. 
Upon confirmation of all inclusion/exclusion criteria, eligible subjects will be randomized on 
Day 1. Study treatment will be administered following assessment of Baseline angiographic 
measures, index of microcirculatory resistance (IMR) and additional coronary physiology 
indices, and blood sample collection (for assessment of peripheral serotonin concentration and 
additional laboratory assessments). Each subject will receive an intravenous (IV) single dose of 
study treatment. Assessment of IMR and additional coronary physiology indices will be repeated 
after administration of study treatment and before the start of the PCI procedure to obtain 
Pre-PCI values. Immediately after completion of PCI, the following assessments will be 
performed to obtain Post-PCI values: Assessment of IMR and additional coronary physiology 
indices, angiographic measures, and collection of blood samples (obtained from the coronary 
ostium and coronary artery distal to the lesion for assessment of coronary artery serotonin 
concentration, as well as venous blood samples for peripheral serotonin concentration and 
additional laboratory assessments) (Figure 2). 
Stage A is an ascending single dose study planned to consist of 2 cohorts. After treatment of each 
cohort in Stage A, a safety/tolerability assessment will be conducted by the Data and Safety 
Monitoring Board (DSMB). Following the safety review of the first cohort in Stage A, the 
DSMB will recommend whether dose escalation to the next planned dose level in Stage A should 
occur; the DSMB may also recommend evaluation of an alternative dose in the second cohort in 
Stage A. Following the safety review of the second cohort in Stage A, the DSMB will 
recommend whether progression to Stage B should occur; the DSMB may also recommend 
evaluation of an alternative dose in an additional third dose cohort in Stage A prior to 
progression to Stage B. After conduct of the final cohort and safety review of Stage A, Stage B 
may begin. Stage B is a parallel treatment group study planned to consist of a placebo group and 
2 active treatment groups (temanogrel doses selected based on safety and tolerability data in 
Stage A). In Stage B, enrollment will consist of no more than 25% elective PCI subjects and 
randomization will be stratified by subject type (elective PCI or PCI for non-ST-elevation 
myocardial infarction [NSTEMI]/unstable angina [UA]). 
Subjects should be treated with aspirin and an oral P2Y12 inhibitor (ie, DAPT) per site standard 
of care; however, subjects in Stage A may only be treated with clopidogrel as the P2Y12 inhibitor 
DAPT component and may not be treated with prasugrel or ticagrelor until after the subject has 
completed study participation. 


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Figure 1:
Schematic Diagram of Study Design
Note: Stage A is an ascending single dose study including 2 planned cohorts with an optional third cohort. After completion of 
Stage A, 2 temanogrel doses will be selected for evaluation in Stage B which will consist of 3 parallel treatment groups 
(2 temanogrel doses and placebo). Dose escalation procedures in Stage A are described in Section 10.11 and procedures for 
transitioning from Stage A to Stage B are described in Section 11.11.


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Figure 2:
Subject Flow of Events
a Diagnostic angiography including confirmation of lesion-related eligibility can be performed prior to randomization at Check-in 
or within 60 days prior to Day 1.
b Can be performed as part of eligibility confirmation/confirmation of suitability for PCI per institutional standards prior to 
randomization at Check-in.
c The final peripheral blood draw is to occur at 24 hours after PCI or at the time of discharge, whichever occurs first. Refer to the 
Schedule of Assessments (Appendix 1) for additional details regarding specific timing and allowable windows for all 
assessments.
CFR, coronary flow reserve; FFR, fractional flow reserve; h, hour; IMR, index of microcirculatory resistance; PCI, percutaneous 
coronary intervention


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3.2. 
Scientific Rationale for Study Design  
The purpose of this Phase 2 study is to assess the safety, tolerability, PK, and PD of IV 
temanogrel in adult subjects undergoing PCI for NSTEMI, UA, or elective PCI. Temanogrel is 
an inverse agonist of the 5-HT2A receptor that inhibits 5-HT-mediated amplification of platelet 
aggregation and vasoconstriction; therefore, it is expected to improve microvascular blood flow 
and provide benefit to patients at risk of MVO, such as those undergoing PCI. 
Temanogrel is being developed to treat and prevent MVO mainly in ACS (STEMI and high-risk 
NSTEMI patients); however, for this first-in-patient and proof-of-mechanism assessment of 
temanogrel in the setting of PCI, only less severe populations undergoing PCI, including 
NSTEMI, UA, and stable angina patients, will be evaluated. In the setting of NSTEMI/UA and 
elective PCI, the effects on the microcirculation are commonly transient and of smaller 
magnitude than in primary PCI for STEMI. IMR is an invasive assessment of the coronary 
microvascular physiology that can provide quantitative and highly sensitive evaluation of 
coronary microcirculation, and increased IMR values Post-PCI have been demonstrated to be a 
strong predictor of MVO-associated myocardial damage, impaired cardiac functional recovery, 
and adverse clinical outcomes in STEMI patients (Fearon 2008, Fearon 2013). Therefore, IMR is 
uniquely suited to detect the beneficial effect of temanogrel in this setting, and in the context of 
the other planned assessments of MVO (including other coronary physiology indices and 
angiographic measures) and myocardial injury, will inform the design and dose selection of 
future clinical studies with temanogrel. 
For the purpose of assessing MVO in this study, IMR will be measured at Baseline (prior to 
administration of study treatment), Pre-PCI (after administration of study treatment and before 
start of PCI procedure), and Post-PCI (upon completion of the PCI procedure). The primary PD 
endpoint is the change from Baseline to Post-PCI measurement of IMR, with increased IMR 
values (resistance in the microcirculation) indicative of MVO. The change in IMR from Baseline 
to Pre-PCI will inform of a potential effect of temanogrel on microcirculation independent from 
the PCI procedure. Additional coronary physiology and angiographic assessments will be 
performed to provide additional information on the vascular effects of temanogrel. 
Serotonin plasma concentrations will be measured in peripheral blood (from blood samples 
drawn by venipuncture or indwelling catheter) and coronary artery (from blood samples drawn 
from the coronary ostium and from coronary artery distal to the lesion) to assess the relationship 
between serotonin release and change in IMR (and potentially other coronary physiology and/or 
angiographic measures), and the effect of temanogrel in this setting. Considering that serotonin 
release requires activation of platelets, the extent of platelet inhibition due to DAPT background 
therapy (including P2Y12 inhibitors) will also be assessed. The aim of these assessments is to 
evaluate the relevance of the serotonin pathway in this setting and to establish the 
proof-of-mechanism for temanogrel. 
Bleeding complications have been associated with an increased risk of subsequent adverse 
outcomes in patients undergoing PCI. Therefore, an important safety measure throughout this 
study is the monitoring of all adverse events including bleeding events which will be classified 
using the Bleeding Academic Research Consortium (BARC) bleeding criteria (Mehran 2011), a 
universal standardized criteria of bleeding severity. 


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This study has been designed as a randomized, double-blind, placebo-controlled study to reduce 
bias and account for placebo effect in the evaluation of the safety and PD of IV temanogrel. 
3.3. 
Rationale for Dose Selection  
Preliminary safety, tolerability, PK, and PD data from APD791-106 Phase 1 clinical study 
suggests that IV temanogrel administered at single doses up to 40 mg demonstrated an 
acceptable safety and tolerability profile in healthy adult humans. When administered over a 
period of 5 minutes, the 40 mg IV temanogrel dose exhibited a similar maximal exposure (mean 
Cmax 1840 ± 349 ng/mL) and lower overall exposure (mean area under the plasma concentration 
vs. time curve from time zero to the time of the last quantifiable plasma sample [AUC0-t] 
732 ± 163 ng/mL/h) compared with the highest single oral dose (320 mg) of temanogrel studied 
in the absence of DAPT (mean Cmax 1610 ± 473 ng/mL, AUC0-t 2831 ± 1146 ng/mL/h). 
A dose-dependent inhibition of 5-HT-mediated platelet aggregation was observed with near 
maximal inhibition at doses of 20 mg and greater over 4 hours after dosing. Previously, a 
near-complete attenuation of 5-HT-mediated vasoconstriction in the presence of ketanserin (a 
5-HT2A receptor antagonist with receptor binding affinity and functional activity similar to 
temanogrel) was observed at a concentration of 200 nM. In the Phase 1 study of single doses of 
IV temanogrel, all subjects who received the 40 mg IV temanogrel maintained exposure above 
this concentration during the 1 hour following dosing, which should ensure an appropriate 
coverage over the duration of a PCI procedure. 
Thus, in the current study single 20 and 40 mg doses of IV temanogrel will be administered to 
evaluate a range of doses across concentrations expected to elicit meaningful PD effects in the 
setting of PCI. In the IV and oral Phase 1 clinical studies, adverse events, cardiovascular 
parameters, and laboratory tests were closely monitored across the exposures associated with 
these doses, and no notable adverse effects occurred. 


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4. 
STUDY POPULATION  
4.1. 
Inclusion Criteria  
Subjects must meet ALL of the following inclusion criteria to be eligible for enrollment into the 
study: 
1. Stable angina patients suitable for elective PCI or patients suitable for PCI for diagnosis 
of NSTEMI/UA. NSTEMI/UA patients are to be consistently hemodynamically stable 
until the time of PCI and have a thrombolysis in myocardial infarction (TIMI) flow 
Grade (TFG) 2 or 3 on the diagnostic angiography 
2. Target lesions for PCI must appear suitable for stenting as confirmed on the diagnostic 
angiography. Acceptable lesions cannot be in the left main artery or in a vein or arterial 
graft, or be a chronic total occlusion or in-stent restenosis. Two or more sequential 
lesions may be treated in the same artery, as long as they are treated in the same session 
and at least one of the lesions meets inclusion criteria 
• For elective PCI patients and non-urgent NSTEMI/UA patients (PCI > 12 hours after 
diagnosis), the lesion must be located in a ≥ 2.75 mm diameter coronary artery; the 
lesion must also be ≥ 18 mm long and require the use of one or more stents that in 
total must be ≥ 20 mm long. 
• For NSTEMI patients treated with PCI urgently (within 12 hours after diagnosis), the 
coronary artery diameter of the culprit lesion must be ≥ 2.75 mm.  
3. 30 to 80 years of age, inclusive 
4. Female subjects must not be lactating at the time of Screening 
5. Females must meet criterion a and males must meet criterion b to qualify for the study: 
a. Females must not be of childbearing potential by one of the following: 
• 
Postmenopausal, defined as no menses for 12 months without an alternative 
medical cause 
• 
Permanent sterilization procedure, such as hysterectomy, bilateral salpingectomy, 
or bilateral oophorectomy 
b. Males with pregnant or non-pregnant female partners of childbearing potential must 
agree to using a condom during treatment and for 90 days following treatment 
6. Body mass index 18.0 to 40.0 kg/m2, inclusive 
7. Willing to participate in the study and provide written informed consent 
4.2. 
Exclusion Criteria  
Subjects who meet ANY of the following exclusion criteria will not be eligible for enrollment 
into the study: 
1. Planned or anticipated use of rotational atherectomy/ablation or shockwave therapies 
during the PCI procedure  


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2. Any history of stroke, seizure, intracranial bleeding, or intracranial aneurysm 
3. Transient ischemic attack within the 6 months prior to Screening 
4. History of major trauma, major surgery, and/or clinically significant head injury or 
hemorrhage within the last 6 months of Screening 
5. Any STEMI within 10 days of Screening or STEMI within the target vessel territory 
within the last 4 months of Screening (eg, a patient with a NSTEMI because of a lesion in 
a diagonal may not be included if there is a history of anterior STEMI due to left anterior 
descending artery [LAD] lesion that occurred within the last 4 months) 
6. Known history of heart failure with reduced ejection fraction (HFrEF) defined as left 
ventricular ejection fraction ≤ 40% prior to current hospital admission 
7. Vasculitis within the last 6 months of Screening 
8. Known contraindication or allergy to heparin (eg, history of heparin-induced 
thrombocytopenia [HIT]), any antiplatelet agents (ie, aspirin, P2Y12 inhibitors), or 
adenosine 
9. Use of any strong inhibitors or inducers of cytochrome P450 (CYP)3A4 or 
P-glycoprotein (examples include, but are not limited to, St. John’s wort, ketoconazole, 
itraconazole, clarithromycin, erythromycin, rifampicin, and verapamil) within 14 days or 
5 half-lives (whichever is longer), relative to Check-in. Intra-arterial use of verapamil for 
subjects undergoing radial artery PCI is permitted. 
10. Consumption of grapefruit within 3 days of Check-in 
11. Use of medications affecting the serotonin system (eg, selective serotonin reuptake 
inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRI], atypical [second 
generation] antipsychotics possessing 5-HT2A pharmacology, or any other serotonergic 
agents possessing 5-HT2A pharmacology [eg, the triazolopyridine antidepressant, 
trazodone]) within 14 days of Check-in 
12. Treatment with cangrelor or glycoprotein IIb/IIIa inhibitors within 24 hours of Check-in 
13. Need for chronic oral anticoagulant (eg, warfarin or direct oral anticoagulants [DOACs], 
including direct oral thrombin inhibitors) for any condition (eg, treatment of atrial 
fibrillation, deep vein thrombosis, or prosthetic cardiac valve) within 1 week of Check-in 
14. For subjects in Stage A ONLY: Use of prasugrel or ticagrelor within 14 days of Check-in 
15. Any other surgeries or interventional procedures planned or anticipated throughout the 
duration of the study 
16. Any history or clinical manifestation of endocrine, allergic, dermatological, hepatic, 
renal, hematological, pulmonary, gastrointestinal, neurological or psychiatric disorder, or 
malignancy within 1 year of study participation (with the exception of treated basal cell 
carcinomas), that in the opinion of the Investigator would prevent the individual from 
participating in the study due to risk to the scientific validity of study assessments or to 
the patient’s personal well-being 


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17. Abnormal clinical chemistry, hematology, or physical finding at Screening or 
electrocardiogram (ECG) at Check-in that in the opinion of the Investigator are clinically 
significant and that would prevent the individual from participating in the study due to 
risk to the scientific validity of study assessments or to the patient’s personal well-being 
18. Clinically significant renal insufficiency (ie, serum creatinine > 2.5 mg/dL or estimated 
glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2; calculated using the Chronic 
Kidney Disease Epidemiology Collaboration [CKD-Epi] equation) at Check-in or within 
6 months of Check-in 
19. Impaired hemostasis (eg, thrombocytopenia [platelet count < 100,000/μL] at Check-in; 
past or present bleeding disorder, sickle cell or other platelet disorders, or carcinoid 
disorder) 
20. Abnormal sodium, potassium, or hemoglobin values at Check-in that in the opinion of the 
Investigator are clinically significant and that would prevent the individual from 
participating in the study due to risk to the scientific validity of study assessments or to 
the patient’s personal well-being 
21. Known human immunodeficiency virus (HIV) or hepatitis infection, or known history of 
cirrhosis 
22. Known history of alcohol or substance use disorder that is considered clinically 
significant per the judgement of the Investigator and that would represent risk to the 
scientific validity of study assessments or the patient’s personal well-being 
23. Previous participation in a study with temanogrel 
24. Subjects who have received any investigational device or investigational drug within 
30 days, or 5 half-lives of the investigational drug (whichever is greater) prior to 
Screening 
25. Hypersensitivity to temanogrel or any of the excipients or placebo compounds 
 


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5. 
SUBJECT RESTRICTIONS  
5.1. 
Restricted Medications  
Subjects are to follow the medication restrictions outlined in the Inclusion (Section 4.1) and 
Exclusion (Section 4.2) criteria throughout study participation (until the Follow-Up phone call), 
unless otherwise specified. The following concomitant medications are restricted from the time 
of consent as specified below: 
• Strong inhibitors or inducers of CYP3A4 or P-glycoprotein for at least 6 hours after 
administration of study treatment. Intra-arterial use of verapamil for subjects 
undergoing radial artery PCI is permitted. Additional information about CYP3A4 
inhibitors and inducers can be found at the following FDA website: 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-
interactions-table-substrates-inhibitors-and-inducers#table3-1 
• Cangrelor or glycoprotein IIb/IIIa inhibitors are restricted until after completion of 
study participation, unless needed as a bail out therapy in the clinical judgement of 
the investigator (or designee) for treatment of no reflow or acute stent thrombosis. 
• Oral anticoagulants (eg, warfarin or DOACs including oral direct thrombin inhibitors) 
for at least 6 hours after administration of study treatment. 
• Use of medications affecting the serotonin system (eg, SSRIs, SNRIs, atypical 
[second generation] antipsychotics possessing 5-HT2A pharmacology, or any other 
serotonergic agents possessing 5-HT2A pharmacology [eg, triazolopyridine 
antidepressant, trazodone]) for at least 24 hours after administration of study 
treatment. 
• For subjects in Stage A: Prasugrel or ticagrelor until after completion of the study 
participation. 
5.2. 
Dietary Restrictions  
Subjects must avoid grapefruit prior to Check-in as described in Section 4.2 and continue to 
avoid grapefruit through the completion of scheduled blood draws. 
Subjects for whom Screening is not on the same day as Check-in should be advised to avoid food 
high in indoles (eg, avocado, banana, tomato, plum, walnut, pineapple, and eggplant) as well as 
alcohol, tobacco, tea, and coffee for a minimum of 24 hours, and ideally 3 days, prior to the PCI 
procedure to increase the accuracy of serotonin concentration assessments. On Day 1 at 
Check-in, all subjects should be asked if they consumed foods high in indoles in the preceding 
24 hours and/or 3 days and their response should be documented in the source and electronic 
case report form (eCRF). Blood samples for serotonin concentration assessment will be taken for 
all subjects, even if dietary restrictions are not adhered to. Subjects should be advised to follow 
the above restrictions through the completion of scheduled blood draws. 


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6. 
STUDY TREATMENT  
6.1. 
Study Treatment(s) Administered  
Study treatments include a pharmaceutical form of the active substance being tested (temanogrel) 
and the placebo being used as a reference (reference therapy). Placebo and temanogrel treatments 
will be diluted to the same volume within each cohort or group to blind study staff to treatment 
assignment. Study treatments are listed in Table 1. 
Table 1: 
Study Treatments 
Study Treatment 
Dose(s) 
Mode of 
Administration 
Frequency 
Formulation 
Temanogrel  
(Stage A: Dose Cohort 1) 
20 mg 
IV 
Single dose 
IV injectable 
solution 
Temanogrel  
(Stage A: Dose Cohort 2) 
40 mg 
IV 
Single dose 
IV injectable 
solution 
Temanogrel  
(Stage A: Dose Cohort 3 
[optional]) 
X mg 
IV 
Single dose 
IV injectable 
solution 
Temanogrel  
(Stage B: Dose Group 1) 
(20, 40, or X) mg 
IV 
Single dose 
IV injectable 
solution 
Temanogrel  
(Stage B: Dose Group 2) 
(40 or X) mg 
IV 
Single dose 
IV injectable 
solution 
Placebo (Stage A and B)a          NA 
IV 
Single dose 
IV injectable 
solution 
a Placebo will follow the same dilution instructions as temanogrel. 
IV, intravenous; NA, not applicable; X mg, dose to be determined based on the results of prior dose cohorts if an optional cohort 
is warranted 
6.2. 
Identity of Study Treatments  
6.2.1. 
Temanogrel  
Temanogrel will be provided as a 25 mg/mL strength, 8 mL fill of a clear solution (colorless to 
tinted solution, essentially free from visible particles) in a single-use 10 mL clear glass vial with 
a grey rubber stopper and flip-off aluminum seal. Each 10 mL vial will be labelled and placed 
into an individual vial carton. Each vial carton will be labelled and secured via tamper evident 
seals. 
6.2.2. 
Placebo  
Arena will supply placebo for temanogrel injectable solution. Placebo will be provided as an 
8 mL fill of a clear solution (colorless to tinted solution, essentially free from visible particles) in 
a single-use 10 mL clear glass vial with a grey rubber stopper and flip-off aluminum seal. Each 
10 mL vial will be labelled and placed into an individual vial carton. Each vial carton will be 
labelled and secured via tamper evident seals. The placebo drug product has the same pH 
(3.5 ± 0.3) and contains the same excipients as the temanogrel injectable solution (active) with 
additional dextrose, to adjust for the tonicity loss associated with absence of active. 


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6.3. 
Dosage and Administration  
The study treatment will arrive at the site blinded and will be administered in a blinded fashion 
to the subjects. A delegated study staff will be responsible for providing temanogrel or placebo 
to study personnel for administration as per the randomization scheme. For each subject, study 
treatment preparation will occur after the subject has been randomized. All doses will be diluted 
to a final volume of 25 mL. Each subject will be dosed intravenously with 5 mL of this prepared 
volume. Dilution instructions will be provided in a separate pharmacy manual.  
An aliquot of the prepared dilution (3 mL) will be collected and appropriately stored as described 
in the Pharmacy Manual. Aliquots may be analyzed to confirm dose concentration.  
Study treatment will be administered intravenously. All enrolled subjects will receive a single IV 
dose of study treatment. Temanogrel dose to be administered to Cohort 1 of Stage A will be a 
20 mg IV bolus (to be administered in the forearm over a period of not less than 5 minutes). 
Planned doses administered to subsequent cohort(s) in Stage A and selected doses for Stage B 
may be adjusted depending on the safety and tolerability data of previously treated subjects. 
Doses in this study will not exceed 40 mg. Placebo administration duration, administration 
location, and volume will match that of temanogrel. Hour 0 will correspond to the start of the IV 
bolus administration. 
6.3.1. 
Instructions for Missed Dose(s)  
Subjects will be administered a single dose of study treatment. No missed doses are expected. 
6.3.2. 
Dose Interruptions  
Subjects will be administered a single dose of study treatment. Therefore, there will not be any 
dose interruptions. 
6.4. 
Method of Assigning Subjects to Treatment  
Each subject will be assigned a unique identification number upon Screening. Eligible subjects 
will be centrally randomized into the study using an interactive response technology (IRT) 
system. Subjects who complete the study Screening assessments and meet all the eligibility 
criteria will be assigned a unique randomization identification number at the time of study 
treatment administration, different from the screening number, and will receive the 
corresponding product according to a randomization scheme. 
Subject identification numbers will be 12 characters in length, including dashes, 
202-CCSS-XXX. The first 3 digits represent the study number, the 4 digits following the first 
dash represent the combination of country code (CC) and the site number (SS), and the last 
3 digits represent the subject number. Subject numbers will be assigned strictly sequentially at 
every site as subjects become eligible for enrollment, starting from 001. 
In Stage A, eligible subjects will be randomly assigned to study treatment in a 2:1 ratio 
(temanogrel:placebo). In Stage B, eligible subjects will be randomly assigned to study treatment 
in a 1:1:1 ratio (20 mg:40 mg:placebo), stratified by subject type (elective PCI or PCI for 
NSTEMI/UA). 


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6.5. 
Blinding  
The study treatment will arrive at the site blinded and will be administered in a blinded fashion 
to the subjects. The Investigator and other clinical staff will be blinded and will not be unblinded 
unless needed for safety reasons.  
Individuals who are part of the Sponsor’s safety team (who are not otherwise involved with 
study conduct) may be unblinded to the treatment (eg, for the purpose of regulatory reporting).  
Representatives from the bioanalytical lab responsible for analyzing PK samples during the study 
will be unblinded to treatment assignments. These individuals will not be involved in the 
management of the study and will not have access to other subject data.  
Treatment assignments should remain blinded unless that knowledge is necessary to determine 
subject emergency medical care. In case of an emergency, the Investigator has the sole 
responsibility for determining if unblinding of a subject’s treatment assignment is warranted to 
provide appropriate medical care. Subject safety must always be the first consideration in making 
such a determination. The IRT is programmed with blind-breaking instructions to guide the 
Investigator on how to obtain treatment assignment in the event of an emergency unblinding.  If 
a subject’s treatment assignment is unblinded, the Sponsor must be notified within 24 hours after 
breaking the blind. The date and reason the blind was broken must be recorded in the source 
documentation and eCRF, as applicable. 
Procedures for breaking of the blind as part of a DSMB review are described in the DSMB 
Charter. 
6.6. 
Treatment Compliance  
This is a single dose study. Study treatment administration will be performed in a controlled 
environment by trained, qualified personnel designated by the Investigator. The date and 
start/end time of study treatment administration will be documented. Any changes in study 
treatment procedures will be documented as a protocol deviation. 
6.7. 
Concomitant Therapy  
Any medication (including over-the-counter or prescription medicines, vitamins, and/or herbal 
supplements) or vaccine that a subject receives from 30 days prior to Screening through 
Follow-up phone call must be recorded along with: 
• Reason for use 
• Start and end dates of administration  
• Dosage information including dose and frequency 
Investigators should carefully evaluate local prescribing information of concomitant therapy for 
interactions described in Section 5.1. The Medical Monitor should be contacted if there are any 
questions regarding concomitant therapy. 


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6.7.1. 
Required Concomitant Therapy  
Subjects should be treated with aspirin and an oral P2Y12 inhibitor (ie, DAPT) per standard 
institutional practices. Subjects may enter the study while on background therapy of DAPT; if 
subjects are not on background DAPT therapy on the day of their procedure, DAPT treatment 
should be started prior to the start or during the PCI procedure, per standard institutional 
practices and according to the American College of Cardiology clinical practice guidelines 
(Levine 2016) or the European Society of Cardiology (ESC) guidelines (Neumann 2019). 
Subjects in Stage A may only be treated with clopidogrel as the P2Y12 inhibitor DAPT 
component and may not be treated with prasugrel or ticagrelor until after the subject has 
completed the study participation. Subjects in Stage B can be treated with any P2Y12 inhibitor as 
part of DAPT. Details of DAPT treatment including the time of administration and exact dose of 
aspirin and P2Y12 inhibitors will be captured in the eCRF. 
As part of the IMR assessment, 140 µg/kg/min of adenosine will be infused intravenously for 
each IMR assessment.  
6.7.2. 
Allowed Concomitant Therapy  
Medications deemed by the Investigator to be appropriate and unlikely to interfere with the 
scientific validity of the study or personal wellbeing of the subject and which are not prohibited 
as indicated in inclusion and exclusion criteria and/or in Section 5.1 are permitted. 
Concomitant medications, including prescription or over-the-counter therapeutics, natural 
products, and vitamins, should not be changed during Screening or at any time during the study, 
unless medically necessary; such changes will be captured in the eCRF. 


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7. 
STUDY TREATMENT AND MATERIALS MANAGEMENT  
7.1. 
Packaging and Labeling  
Temanogrel and placebo will be provided as approximately 8 mL of a clear solution in a 
single-use 10 mL clear glass vial with a grey rubber stopper and flip-off aluminum seal. Each 
10 mL vial will be labelled and placed into an individual vial carton. Each vial carton will be 
labelled and secured via tamper evident seal. 
7.2. 
Storage and Handling  
Study treatment must be stored in an appropriate, restricted-access, secure location within a 
temperature range between 15°C to 30°C (59°F to 86°F). The study treatment should be stored 
protected from light during long-term storage, but no special precautions are required for 
short-term handling (< 24 hours). 
The site must maintain a temperature log to document the temperature of study treatment storage 
conditions. Sites may use their own temperature log as long as it captures, at a minimum, the 
following required information: min/max values recorded once daily, protocol ID, site ID, and 
storage location. 
Temperature should be monitored on a daily basis, either by continuous temperature registration, 
or by using a min-max thermometer. A copy of the temperature log should be filed in the 
Investigator Site File or Pharmacy Binder. 
Vials of study treatment should not be used beyond the expiration or retest date printed on the 
study drug label. 
Used and/or partially used vials should be stored separately from the unused study treatment for 
study treatment accountability as allowed by the site’s standard operating procedures. 
Dilutions of temanogrel can be stored refrigerated for up to 24 hours or at room temperature for 
up to 4 hours. Refrigerated solutions must be brought to room temperature prior to 
administration of a dose. 
7.3. 
Preparation  
A separate pharmacy manual will detail the study treatment preparation procedures to be 
followed for this study. Following preparation of study treatment, an aliquot (3 mL) will be 
collected and appropriately stored as described in the Pharmacy Manual. Aliquots may be 
analyzed to confirm dose concentration. 
7.4. 
Study Drug Accountability  
The Investigator or pharmacist (or designee) will keep accurate records of the quantities of the 
study drug (temanogrel and placebo) dispensed. Reasons for any deviation from the expected 
dispensing regimen must also be recorded. Study drug will be reconciled by the Sponsor, 
monitor, or contracted designee before the site is closed. The Investigator agrees to provide 
sufficient access to study drug as required for the reconciliation process to be completed in a 
timely fashion. 


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7.5. 
Study Treatment Retention and Disposal  
All study treatment will be reconciled by the clinical monitor and then returned to the Sponsor or 
destroyed according to applicable country regulations. On-site destruction is permitted following 
all local regulations and in accordance with the site’s SOPs. Final reconciliation will be 
performed at study completion. 


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8. 
REMOVAL OF SUBJECTS FROM THERAPY OR ASSESSMENT  
8.1. 
Discontinuation of Study Treatment  
As this is a single-dose study, subjects are not expected to discontinue from study treatment. 
8.2. 
Discontinuation from the Study  
Subjects may discontinue/be discontinued from the study at any time for any of the following 
reasons: 
• Adverse event 
• Death 
• Pregnancy (Section 10.8.6) 
• Protocol deviation 
• Investigator decision 
• Withdrawal by subject 
• Study termination by Sponsor 
• Other 
A subject may elect to discontinue study participation at any time for any reason without 
prejudice to their future medical care by the physician or at the institution.  
Subjects who are randomized but not subsequently dosed and subjects who discontinue study 
participation will be considered Early Termination subjects. Should a subject become unwilling 
or unable to complete the remaining scheduled PK/PD and safety assessments (individual 
missing data points do not count as early discontinuation), the Follow-Up phone contact should 
be performed as described in protocol Section 9.4 (Early Termination). 
If a subject withdraws consent for any further evaluation, no further evaluation will be 
performed, no additional data should be collected, and samples must be destroyed. The Sponsor 
may retain and continue to use any data collected before such withdrawal of consent. The 
Investigator should make a reasonable attempt to document the specific reason why consent was 
withdrawn. 
8.3. 
Lost to Follow-Up  
Subjects are considered lost to follow-up if all reasonable attempts made by the Investigator and 
study delegated staff to complete the scheduled Follow-Up phone contact with the subject 
failure. A minimum of 3 attempts must be made to contact the subject. Each attempt must be 
documented in the subject’s records (ie, method of communication, times, and dates). If all 
3 attempts fail, site must have receipt of a registered letter sent to the subject as the last attempt 
before considering the subject lost-to-follow-up in the eCRF. 


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8.4. 
Premature Termination of the Study or Study Site  
The Sponsor has the right to terminate this study at any time. Reasons for terminating the study 
may include, but are not limited to, the following: 
• The incidence or severity of adverse events in this or other studies indicates a 
potential health hazard to subjects 
• Subject enrollment is unsatisfactory 
• Upon request of Health Authorities 
The Sponsor will notify the Investigator if the study is placed on hold or if the Sponsor decides 
to discontinue the study. Health authorities and (Independent Ethics Committee[s] [IECs])/ 
(Institutional Review Board[s] [IRBs]) will be informed about the termination of the study in 
accordance with applicable regulations. 
The Sponsor has the right to terminate or replace a study site at any time. Reasons for 
terminating or replacing a study site may include, but are not limited to: 
• Excessively slow recruitment 
• Poor protocol adherence 
• Inaccurate or incomplete data recording 
• Non-compliance with the ICH guideline for GCP 


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9. 
STUDY PERIODS  
9.1. 
Screening and Enrollment  
The Screening period is to occur up to 14 days prior to and/or on the day of the PCI procedure 
(Day −14 to 1). For details of the study Screening and enrollment see the Schedule of 
Assessments (Appendix 1). Potential subjects will provide written informed consent before any 
study-specific procedure is performed. Eligible subjects meeting all inclusion/exclusion criteria 
requirements may be enrolled.  
9.2. 
Treatment Period  
Potential eligible subjects (per initial Screening criteria) will undergo Check-in assessments to 
confirm eligibility on Day 1 (day of PCI procedure) per the Schedule of Assessments 
(Appendix 1), including confirmation of lesion-related eligibility by diagnostic angiography 
(unless performed within 60 days prior to Day 1). These assessments will be performed locally 
and assessed by the Investigator. Upon confirmation that a subject is eligible for study 
participation, the subject will be randomized. 
Following randomization, in cases when diagnostic angiography is not performed at Check-in, 
lesion and vessel characteristics should be assessed as part of Baseline target vessel angiographic 
measures assessment. Similarly, in cases when coronary physiology indices have not been 
assessed at Check-in for confirmation of suitability for PCI per institutional standards, they 
should be assessed at Baseline. For all subjects, Baseline peripheral blood samples will be 
collected. The subject will then be administered study treatment intravenously. 
Zero (0) to 2 minutes after the completion of the IV administration of randomized study 
treatment, a Pre-PCI peripheral blood sample will be drawn followed by measurement of the 
Pre-PCI coronary physiology indices. Once the Pre-PCI coronary physiology indices have been 
measured, the PCI procedure will begin. Vital signs and ECG changes will be monitored 
throughout the procedure per site standard of care and any clinically significant findings will be 
recorded as adverse events in the eCRF but there are no required study-specific assessments 
during the conduct of the PCI procedure. 
Immediately upon completion of the PCI procedure, the following Post-PCI assessments will be 
performed: Blood sampling from the coronary ostium and from coronary artery distal to the 
lesion, coronary physiology indices, target vessel angiographic measures, and peripheral blood 
sampling. Upon completion of all planned assessments and per the site’s standard of care, the 
subject will be transitioned to the step-down unit at the study center. Additional safety 
assessments and blood draws prior to discharge will occur per the Schedule of Assessments 
(Appendix 1). Subjects will be discharged at the Investigator’s discretion based upon clinical 
presentation, but not prior to the collection of all 6-hour Post-PCI assessments. 
9.3. 
Follow-Up Phone Call/End of Study  
Subjects will have one Follow-Up phone call 7 (± 2) days postdose to assess for adverse events. 
For each subject, study participation is completed once the Follow-Up phone call has been 
conducted. The End of Study Date is the date when the last subject completes his/her final 
Follow-Up phone call. 


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9.4. 
Early Termination  
Subjects who are randomized but not subsequently dosed and subjects who discontinue study 
participation will be considered Early Termination subjects. Should a subject become unwilling 
or unable to complete the remaining scheduled PK/PD and safety assessments (individual 
missing data points do not count as early discontinuation), the Follow-Up phone call should be 
performed for subjects who received a dose of randomized study treatment. Site staff should 
work with subjects who withdraw early to obtain as much follow-up data as possible. 


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10. 
STUDY ASSESSMENTS AND PROCEDURES  
10.1. 
Subject Informed Consent  
The Investigator, or a person designated by the Investigator, will obtain written informed consent 
from each subject before any study-specific activity is performed. 
10.2. 
Screening and Eligibility  
Subject eligibility will be assessed based on protocol inclusion and exclusion criteria. Certain 
Screening and eligibility assessments must be performed and/or reviewed on Day 1 prior to 
randomization as part of Check-in assessments per Table 2 and the Schedule of Assessments 
(Appendix 1). All other Screening and eligibility assessments must be completed any time within 
14 days prior to randomization on Day 1, unless otherwise specified (Appendix 1).  
Individuals may qualify for study enrollment following an abnormal laboratory test, vital signs, 
or ECG finding by having that test repeated once with acceptable results as judged by the 
Investigator (or designee). The Investigator may consult with the Medical Monitor as needed. If 
additional retests are considered, the Clinical Lead should be consulted, and the outcome of the 
conversation should be documented. 
10.2.1. 
Rescreening  
Subjects who have not been randomized and do not meet inclusion and/or exclusion criteria may 
be re-consented and re-screened with a new screening number if the Investigator assesses that the 
subject is an appropriate candidate for re-screening. The Investigator may consult with the 
Medical Monitor if there are any questions related to rescreening a subject. Subjects may not be 
rescreened more than once. 
10.2.2. 
Demography and Other Subject Characteristics  
Subject demographic information (ie, year of birth, age at consent, sex at birth, reproductive 
status for female subjects, ethnicity, and race as described by the subject) will be collected. 
10.2.3. 
Prior and Ongoing Therapies  
All medications and procedures conducted within 30 days prior to dosing will be recorded at 
Screening. Updates to medications or procedures prior to study treatment administration should 
be made as needed. 
10.2.4. 
Medical History  
A complete medical history of each subject will be collected and documented during Screening 
to determine subject eligibility. The history should include disease characteristics relevant to the 
study (including date and details of diagnosis, associated interventional procedures and/or 
hospitalizations), social history (eg, tobacco use, alcohol use), recent blood donations (within 
30 days), illnesses, participation in other investigational drug studies, and participation in any 
medical device clinical investigations. 


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10.2.5. 
Clinical Chemistry and Hematology  
Select Check-in clinical chemistry and hematology assessments noted in Appendix 1 and Table 2 
are required to be resulted for eligibility purposes prior to randomization. For those select lab 
assessments, laboratory assessments obtained within 48 hours prior to randomization may be 
referenced for purposes of assessing eligibility. For all other serum chemistry and hematology 
assessments, laboratory assessments collected within 60 days prior to Day 1 and with a panel 
relevantly similar to those listed in Table 2 in the clinical judgement of the Investigator (or 
qualified designee) may be referenced for purposes of assessing eligibility (Section 4.2). 
10.2.6. 
Diagnostic Angiography  
Confirmation of lesion and vessel characteristics is required for eligibility purposes prior to 
randomization. Lesion length should be measured across a distance where stenosis is at least 
20% of the vessel diameter for the entirety of the lesion length. For elective PCI patients and 
non-urgent NSTEMI/UA patients who are undergoing PCI more than 12 hours after diagnosis, 
the lesion must be located in a ≥ 2.75 mm diameter coronary artery; the lesion must also be 
≥ 18 mm long and require the use of one or more stents that in total must be ≥ 20 mm long; and 
TFG must be 2 or 3. For NSTEMI patients undergoing PCI urgently within 12 hours after 
diagnosis, the coronary artery diameter of the culprit lesion must be ≥ 2.75 mm and TFG must be 
2 or 3. Diagnostic angiography including confirmation of lesion-related eligibility can be 
performed prior to randomization at Check-in or within 60 days prior to Day 1, as defined in the 
Schedule of Assessments (Appendix 1). In cases when diagnostic angiography is not performed 
at Check-in, lesion and vessel characteristics should be assessed as part of Baseline target vessel 
angiographic measures assessment prior to administration of study treatment. Diagnostic 
angiography findings used to determine subject eligibility, whether obtained within 60 days prior 
to Day 1 or at Check-in, must be entered in the eCRF. 
10.3. 
Percutaneous Coronary Intervention  
Cardiac catheterization using either trans-radial or femoral artery approach, coronary 
angiography, and PCI with predilation (if applicable) and stent deployment, will be performed in 
line with accepted institutional practice. 
Periprocedural anticoagulation should be achieved with heparin or bivalirudin using standard 
institutional practice for the duration of the procedure only. Prolonging the anticoagulation 
treatment is permitted as bail out therapy for no reflow or acute stent thrombosis only and if 
done, it should be reported as a concomitant medication in the eCRF; any associated adverse 
events should also be reported in the eCRF. 
10.4. 
Pharmacodynamic Assessments  
10.4.1. 
Coronary Physiology Indices  
Assessment of coronary physiology indices will be performed on all randomized subjects and 
will be used to characterize the PD effects of temanogrel. Indices of coronary physiology to be 
assessed in this study include IMR (Section 10.4.1.1), coronary flow reserve (CFR) 
(Section 10.4.1.2), and fractional flow reserve (FFR) (Section 10.4.1.3). Coronary physiology 
indices will be assessed and analyzed as previously described (Fearon 2000) using the 


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Coroventis CoroFlow™ Cardiovascular System, v3.0 or later, and details on the applicable 
methods can be found in a separate operation manual. The coronary physiology indices will be 
assessed at three timepoints: Baseline values will be assessed before study treatment 
administration (after randomization at Baseline, unless already assessed at Check-in for 
confirmation of suitability for PCI per institutional standards; in that case these values can be 
used as Baseline values), Pre-PCI values after completion of study treatment administration, but 
before the PCI procedure, and Post-PCI values within 15 minutes of completion of the PCI 
procedure. Planned timepoints for assessment of coronary physiology indices are provided in the 
Schedule of Assessments (Appendix 1). Additional details regarding the procedures for 
collection and transfer of coronary physiology indices data will be provided in a separate 
operation manual. 
10.4.1.1. Index of Microcirculatory Resistance  
IMR will be used as a primary quantitative assessment of MVO. Briefly, IMR will be obtained 
using an intracoronary pressure and temperature sensor-tipped guidewire by previously described 
thermodilution technique (De Bruyne 2001, Pijls 2002). Thermodilution curves will be obtained 
in triplicate from a hand-held 3 mL rapid injection of room temperature saline at baseline and 
after maximal hyperemia induced by 140 µg/kg/min of adenosine infused intravenously. IMR 
will be defined as the mean distal pressure at maximum hyperemia multiplied by the mean 
hyperemic transit time, as previously described (Fearon 2003, Fearon 2013). IMRcorr (IMR 
corrected for the influence from collateral supply) will be calculated using the following 
equation, to account for the presence of significant epicardial stenosis without the need for 
balloon dilation to measure the coronary wedge pressure (Pw), as previously described (Yong 
2013): 
IMRcorr = Pa × Tmn × [1.34 × Pd/Pa − 0.32] 
where IMRcorr is IMR value corrected for the influence from collateral supply, Tmn is mean 
transit time at maximal hyperemia, Pd is mean distal coronary pressure at maximum hyperemia, 
Pa is mean aortic pressure at maximum hyperemia. 
10.4.1.2. Coronary Flow Reserve  
The coronary flow reserve (CFR) will be calculated from the ratio of baseline (resting) to 
hyperemic mean transit time (CFR = [mean resting transit time/mean hyperemic transit time]). 
10.4.1.3. Fractional Flow Reserve  
The FFR will be calculated from the ratio of distal to proximal mean pressures at maximal 
hyperemia (FFR = [distal coronary pressure/aortic pressure at max hyperemia]). 
10.4.2. 
Angiographic Measures  
Analysis of the target vessel angiographic measures including lesion and vessel characteristics, 
TFG, corrected thrombolysis in myocardial infarction frame count (cTFC), thrombolysis in 
myocardial infarction myocardial perfusion grade (TMPG), and quantitative coronary analysis 
(QCA) will be performed by a blinded central core lab and details on the applicable methods can 
be found in a separate operation manual. The target vessel angiographic measures will be 
assessed at two timepoints: Baseline values will be assessed before study treatment 


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administration (after randomization at Baseline, unless already assessed at Check-in as part of 
diagnostic angiography for lesion-related eligibility; in that case these values can be used as 
Baseline values) and Post-PCI values within 15 minutes of completion of the PCI procedure. 
Planned timepoints for assessment of angiographic measures are provided in the Schedule of 
Assessments (Appendix 1). Detailed instructions regarding the collection and transfer of 
angiographic data will be provided in a separate operation manual. 
10.4.2.1. TIMI Flow Grade  
The TFG, a measure of epicardial perfusion, will be graded on a standard scale from 0 to 3, with 
TFG Grade 0 being no perfusion and TFG Grade 3 complete perfusion (TIMIStudyGroup 1985). 
10.4.2.2. Corrected TIMI Frame Count  
The cTFC, a quantitative index of coronary flow, will be calculated based upon the number of 
cine-frames that the intracoronary dye requires to reach distal coronary landmarks (Gibson 2000, 
Kunadian 2009). 
10.4.2.3. TIMI Myocardial Perfusion Grade  
The TMPG (also known as myocardial blush grade [MBG]), is a measure of myocardial 
perfusion in the capillary bed at the tissues level following contrast injection into the coronary 
artery. TMPG will be graded on a scale from 0 to 3, with TMPG Grade 0 being no “blush” and 
TMPG Grade 3 normal “blush” (Gibson 2000). 
10.4.2.4. Quantitative Coronary Analysis  
QCA will be used to assess the diameter of the coronary artery distal to the lesion. Images of the 
artery will be taken 1 to 2 cm distally to the distal end of the stent used for the treatment of the 
qualifying lesion (images will be taken in the same area at all timepoints, avoiding bifurcations) 
and quantified by the angiographic core lab. 
10.4.3. 
Markers of Myocardial Injury  
CK, creatine kinase-myocardial band (CK-MB), and cTn will be measured as markers of 
myocardial injury (Table 2). Detailed instructions regarding blood sample collection, processing, 
shipping, and analysis for markers of myocardial injury will be provided in a separate laboratory 
manual. 
10.4.3.1. Creatine Kinase  
Blood samples for CK will be collected as specified in the Schedule of Assessments 
(Appendix 1). 
10.4.3.2. Creatine Kinase-Myocardial Band  
Blood samples for CK-MB will be collected as specified in the Schedule of Assessments 
(Appendix 1). 


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10.4.3.3. Cardiac Troponin  
Blood samples for cTn (high-sensitive cardiac troponin T [hs-cTnT] and cardiac troponin I 
[cTnI]) will be collected as specified in the Schedule of Assessments (Appendix 1). cTn will 
serve as a cardiac biomarker for assessment of procedural myocardial injury based on the 4th 
universal definition of myocardial infarction (Thygesen 2018).  
10.4.4. 
Markers of Inflammation  
The following markers of inflammation will be measured: Highly sensitive C-reactive protein 
(hs-CRP) and pentraxin (PTX-3), and cytokines (interleukin [IL]-1, IL-6, IL-8, IL-10, and tumor 
necrosis factor alpha [TNF-α]) (Table 2). Blood samples for markers of inflammation will be 
collected as specified in the Schedule of Assessments (Appendix 1). Detailed instructions 
regarding blood sample collection, processing, shipping, and analysis will be provided in a 
separate laboratory manual. 
10.5. 
Pharmacokinetic Assessments  
Blood samples for plasma PK analysis of temanogrel, AR295980, and AR295981 will be 
collected for all subjects at specified timepoints according to the Schedule of Assessments 
(Appendix 1). Blood samples will be obtained by peripheral venipuncture or, preferably, using 
an indwelling catheter (central line can be used if available). Clock time will be documented for 
each PK blood sample. Collected plasma PK samples may also be stored for up to 3 years after 
the closing of the study and used for profiling of drug binding proteins, bioanalytical method 
validation purposes, stability assessments, or to assess other actions of temanogrel (and/or its 
metabolites) with plasma constituents or for context pertaining to safety events arising during or 
after the study. 
Detailed instructions regarding sample collection, processing, and shipping will be provided in a 
separate laboratory manual. 
During conduct of each cohort in Stage A and during all conduct of Stage B, drug concentration 
information that may unblind the study will not be reported to investigative sites or blinded 
personnel. 
10.6. 
Serotonin  
Peripheral blood samples and coronary artery blood samples will be collected as described in 
Section 10.6.1 and Section 10.6.2.  
10.6.1. 
Peripheral Serotonin  
Blood samples for assessment of peripheral serotonin concentration will be collected as specified 
in the Schedule of Assessments (Appendix 1). Blood samples will be obtained by peripheral 
venipuncture or preferably using an indwelling catheter (central line can be used if available). 
Detailed instructions regarding blood sample collection, processing, shipping, and analysis will 
be provided in a separate laboratory manual. 


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10.6.2. 
Coronary Artery Serotonin  
Blood samples for assessment of coronary artery serotonin concentration will be collected as 
specified in the Schedule of Assessments (Appendix 1). Blood samples will be obtained from the 
coronary ostium and from the coronary artery distal to the lesion using an aspiration catheter 
(such as Export Advance™ thrombus aspiration catheter). Detailed instructions regarding blood 
sample collection, processing, shipping, and analysis will be provided in a separate laboratory 
manual. 
10.6.3. 
Future Biomarker Research  
Where allowed by the regulatory authorities and if the subject has granted consent, residual 
plasma from samples collected to measure serotonin may be stored for up to 10 years after the 
closing of the study. Samples will be stored according to local regulations for study at a facility 
selected by the Sponsor to enable potential future analysis of biomarkers with the aim to further 
understand the efficacy, safety, and/or mechanism of action of temanogrel. Tubes will be 
identified with a barcode using an appropriate label. No diseases/conditions, DNA, or RNA will 
be the focus of these analyses. Samples will not be submitted to a public database. The Sponsor 
and CROs involved in the clinical conduct and analyses of the samples/data will have access to 
the samples and/or the data that result from the analysis, if performed. At any time, the subjects 
can contact the clinical staff to request destruction of their residual samples after the required 
assessments are completed. 
10.7. 
P2Y12 VerifyNow Assay  
Blood samples for assessment of P2Y12 inhibition of platelet activity using the P2Y12 VerifyNow 
assay will be collected as specified in the Schedule of Assessments (Appendix 1). Blood sample 
collection, processing, and analysis will be conducted per the VerifyNow Reference Guide 
(ACCRIVA 2020a, ACCRIVA 2020b). 
10.8. 
Safety Assessments  
Safety assessments will include adverse events, vital signs (systolic and diastolic blood pressure, 
heart rate, respiratory rate, and body temperature), clinical laboratory tests, ECGs, and physical 
examinations. Planned timepoints for all safety assessments are indicated in the Schedule of 
Assessments (Appendix 1). If Screening and Check-in do not occur on the same day (Day 1), 
safety assessments will be repeated on Day 1 prior to randomization. Safety assessments will 
also be repeated prior to discharge. Subjects will be discharged at the discretion of the 
Investigator based upon the clinical presentation. 
10.8.1. 
Vital Signs  
Vital signs measurements will include blood pressure, heart rate, body temperature, respiratory 
rate, and body temperature. Vital signs will be assessed at the timepoints indicated in the 
Schedule of Assessments (Appendix 1). If Screening and Check-in do not occur on the same day 
(Day 1), vital signs will be repeated on Day 1 prior to randomization.  
Subjects should be resting in the supine or seated position for at least 5 minutes prior to 
collection of vital signs. Vital signs will be measured prior to any blood draws that occur at an 
overlapping timepoint.  


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Vital signs monitoring during catheterization procedures will be conducted per site standard of 
care and any clinically significant findings will be recorded as adverse events in the eCRF. 
10.8.2. 
Physical Examinations  
A physical examination will be performed by a licensed physician or designee per the site's 
standard of care at Screening. A symptom-based physical exam will be performed prior to 
discharge. 
10.8.3. 
Electrocardiography  
ECGs extractions will be collected during the study as outlined in the Schedule of Assessments 
(Appendix 1).  
ECGs will be recorded from a 12-lead ECG machine. ECGs will be captured, recorded, and 
analyzed according to the ECG Procedure Manual. Parameters to be provided on the confirmed 
read for each safety ECG are heart rate (HR), RR, PR, QRS, QT, corrected QT interval (QTc), 
corrected QT interval using Bazett’s formula (QTcB), and corrected QT interval using 
Fridericia’s formula (QTcF). It is recommended to collect ECGs at least 30 minutes after the end 
of the subject’s most recent meal. All ECGs will be recorded with subjects in supine position. 
Supine rest time prior to ECGs should be at least 5 minutes. 
The Investigator will be responsible for review and interpretation of ECGs on site for eligibility 
purposes, and for determining if the ECG is normal, abnormal clinically insignificant, or 
abnormal clinically significant and recording any clinically relevant worsening from Baseline 
occurring during the study in the adverse event section of the eCRF. ECGs will also be analyzed 
by the core lab. Both local and central reports must be filed with the source documents. 
ECG monitoring during catheterization procedures is to occur per site standard of care and any 
clinically significant findings will be recorded as adverse events in the eCRF. 
10.8.4. 
Clinical Laboratory Assessments  
Refer to Table 2 for the list of clinical laboratory tests to be performed and the Schedule of 
Assessments (Appendix 1) for timing and frequency for each test. All clinical laboratory tests 
performed prior to randomization will be analyzed at local laboratories. All laboratory 
assessments conducted after randomization will be analyzed at the central laboratory, with the 
exception of VerifyNow testing which will be done locally. Details regarding clinical laboratory 
sample collection, preparation, and shipment of central lab samples will be provided in the 
laboratory manual by the central laboratory. Lab results that are invalid, or appear to be invalid, 
should be repeated when possible. If lab tests used to determine subject eligibility are invalid, the 
tests may be repeated to determine subject eligibility (ie, it is not required to screen-fail a subject 
prior to repeating the lab test). 
Central laboratory reports and, when applicable, local laboratory reports used for Screening and 
eligibility purposes must be filed with the source documents. The Investigator must review all 
the laboratory reports from the local and central laboratory, document this review, and record 
any clinically relevant worsening from Baseline occurring during the study in the adverse event 
section of the eCRF. Clinically significant abnormal laboratory findings are those that are not 
associated with the underlying disease, unless judged by the Investigator to be more severe than 


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expected for the subject’s condition. All laboratory tests with values considered clinically 
significantly abnormal during participation in the study should be repeated until the values return 
to normal or Baseline or are no longer considered clinically significant by the Investigator or 
Medical Monitor. 
In cases when laboratory values from non-protocol-specified assessments are performed at the 
institution’s local laboratory and result in a change in subject management or are considered 
clinically significant by the Investigator (eg, adverse event or dose modification), then the details 
must be documented in the appropriate eCRF. 


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Table 2: 
Clinical Laboratory Tests 
Coagulation 
Activated partial thromboplastin time (aPTT) 
International Normalized Ratio (INR) 
Prothrombin time (PT) 
Hematology 
Hematocrit 
Hemoglobina  
Mean corpuscular hemoglobin (MCH) 
Mean corpuscular hemoglobin concentration (MCHC) 
Mean corpuscular volume (MCV) 
Platelet counta 
Red blood cell (RBC) count  
White blood cell (WBC) count with differential 
Serum Chemistry 
Alanine aminotransferase (ALT) 
Albumin 
Alkaline phosphatase (ALP) 
Aspartate aminotransferase (AST) 
Bicarbonate  
Blood urea nitrogen (BUN) 
Calcium 
Chloride 
Creatininea 
Glucose 
Lactate dehydrogenase (LDH) 
Phosphorus 
Potassiuma 
Sodiuma 
Thyroid-stimulating hormone (TSH) 
Total bilirubin 
Direct bilirubin 
Total cholesterol 
Markers of Myocardial Injury 
Markers of Inflammation 
Cardiac troponin I (cTnI) 
CK-myocardial band (CK-MB) 
Creatine kinase (CK) 
High-sensitivity cardiac troponin T (hs-cTnT) 
Cytokines (interleukin [IL]-1, IL-6, IL-8, IL-10, tumor 
necrosis factor alpha [TNF-α]) 
Highly sensitive C-reactive protein (hs-CRP) 
Pentraxin-3 (PTX-3) 
Additional Assessments 
P2Y12 VerifyNow 
Serotonin 
Drugs of Abuseb  
Amphetamine, barbiturates, benzodiazepines, cocaine, marijuana, methadone, methamphetamine, 
methylenedioxymethamphetamine, opiate, oxycodone, phencyclidine 
a Required to be resulted for eligibility purposes prior to randomization. Labs obtained within 48 hours prior to randomization 
may be referenced for purposes of assessing eligibility. For all other serum chemistry and hematology assessments, laboratory 
assessments collected within 60 days prior to Day 1 and with a panel relevantly similar to those listed (per the clinical 
judgement of the Investigator [or qualified designee]) may be referenced for purposes of assessing eligibility. 
b It is not required to result the urine drug screen prior to randomization. Urine drug screen must be collected prior to discharge. 


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10.8.4.1. Clinical Chemistry, Hematology, and Coagulation  
Clinical chemistry, hematology, and coagulation parameters that will be assessed during the 
study are identified in Table 2. Blood samples will be collected as defined in the Schedule of 
Assessments (Appendix 1). 
10.8.4.2. Drugs of Abuse  
A standard urine drug screen (Table 2) will be performed. It is not required to result the urine 
drug screen prior to randomization. If urine samples for urine drug screen cannot be obtained 
prior to study treatment administration due to the timing of events as required by subject safety 
considerations, then it can be obtained after study treatment administration and prior to 
discharge. 
10.8.5. 
Adverse Events  
10.8.5.1. Definitions  
10.8.5.1.1. Adverse Event  
An adverse event is any untoward medical occurrence that does not necessarily have a causal 
relationship with this treatment. An adverse event can therefore be any unfavorable and 
unintended sign, symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product. 
Adverse events can include, but are not limited to, any of the following: 
• Unfavorable changes in general condition 
• Subjective or objective signs/symptoms 
• Concomitant disease or accidents 
• Clinically relevant adverse changes in laboratory parameters over the course of the 
study 
• Pre-existing conditions that worsen in severity, increase in frequency, or have new 
signs/symptoms 
10.8.5.1.2. Serious Adverse Event  
An adverse event should be classified as a serious adverse event (SAE) if it meets one of the 
following criteria: 
Fatal: 
The adverse event resulted in death. 
Life-threatening: 
The adverse event placed the subject at immediate risk of death. This 
classification does not apply to an adverse event that hypothetically 
might cause death if it were more severe. 
Hospitalization: 
The adverse event required or prolonged an existing inpatient 
hospitalization. Hospitalizations for elective medical or surgical 
procedures or treatments planned before the signing of informed 


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consent in the study or routine check-ups are not SAEs by this 
definition. 
Disabling/ 
incapacitating: 
The adverse event resulted in a persistent or significant incapacity or 
substantial disruption of the subject’s ability to conduct normal life 
functions. 
Congenital anomaly 
or birth defect: 
An adverse outcome in a child or fetus of a subject exposed to the 
study treatment before conception or during pregnancy. 
Medically 
significant: 
The adverse event did not meet any of the above criteria but could have 
jeopardized the subject and might have required medical or surgical 
intervention to prevent one of the outcomes listed above or involves 
suspected transmission via a medicinal product of an infectious agent. 
10.8.5.1.3. Adverse Drug Reaction  
An adverse drug reaction (ADR) in the pre-approval clinical experience with a new medicinal 
product or its new usages, particularly as the therapeutic dose(s) may not be established, is any 
noxious and unintended response to a medicinal product related to any dose. The phrase 
“responses to a medicinal product” means that a causal relationship between a medicinal product 
and an adverse event is at least a reasonable possibility (ie, the relationship cannot be ruled out). 
10.8.5.1.4. Adverse Events of Special Interest  
Based on the mechanism of action of temanogrel and prior experience with other agents acting 
via a similar mechanism, potential adverse events of special interest may be identified. In 
addition to appropriate reporting of these events as an adverse event or SAE, supplementary 
detailed information may be collected. 
10.8.5.1.5. Severity  
The severity of each adverse event will be assessed at the onset by a nurse/or physician. When 
recording the outcome of the adverse event the maximum severity of the adverse event 
experienced will also be recorded. The severity of each adverse event will be graded according to 
the Common Terminology Criteria for Adverse Events [version 5.0]: 
Grade 1: 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
Grade 2: 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental activities of daily living. 
Grade 3: 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, 
limiting self-care activities of daily living (eg, preparing meals, 
shopping for groceries or clothes, using the phone, managing money). 
Grade 4: 
Life-threatening consequences, urgent intervention indicated. 
Grade 5: 
Death related to adverse event. 


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10.8.5.1.6. Relationship  
The Investigator is obligated to assess the relationship (causal relationship) between the study 
treatment and each occurrence of each adverse event. The adverse event relationship (causal 
relationship) to study treatment must be characterized as one of the following categories: 
Not Related: 
The adverse event does not follow a reasonable temporal sequence from 
administration of the drug, does not abate upon discontinuation of the 
drug, does not follow a known or hypothesized cause-effect 
relationship, and (if applicable) does not reappear when the drug is 
reintroduced, furthermore, there may exist a clear alternative medical 
explanation (ie, underlying disease state) or association with study 
procedure or study conduct. 
Unlikely Related: 
The temporal association between the adverse event and the drug is 
such that the drug is not likely to have any reasonable association with 
the adverse event. 
Probably Related: 
The adverse event follows a reasonable temporal sequence from 
administration of the drug and cannot be reasonably explained by the 
known characteristics of the subject’s clinical state, environmental, or 
toxic factors, or other modes of therapy administered to the subject. 
Related: 
The adverse event follows a reasonable temporal sequence from 
administration of the drug, abates upon discontinuation of the drug, 
follows a known or hypothesized cause-effect relationship, and (if 
appropriate) reappears when the drug is reintroduced. 
The Investigator will use clinical judgment to determine the relationship. Alternative causes, 
such as underlying disease(s), concomitant therapy, and other risk factors, as well as the 
temporal relationship of the event to the study treatment administration should be considered and 
investigated. The Investigator should consult the current edition of the IB and the Product 
Information of marketed products within the drug class, when applicable. For each adverse 
event, the Investigator must document in the medical notes that he/she has reviewed the adverse 
event and has provided an assessment of causality. There may be situations in which an SAE has 
occurred and the Investigator has minimal information to include in the initial report to the 
Sponsor; however, the Investigator should always make an initial assessment of causality for 
every event before the initial transmission of the SAE to the Sponsor. The Investigator may 
change his/her opinion of causality based on subsequent receipt of information and send an SAE 
follow-up report with the updated causality assessment. The causality assessment is one of the 
criteria used when determining regulatory reporting requirements. 


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10.8.5.2. Eliciting, Recording, and Reporting Adverse Events  
10.8.5.2.1. Eliciting Adverse Events  
Subjects will be instructed that they may report adverse events at any time. An open-ended or 
nondirected method of questioning should be used at each study visit to elicit the reporting of 
adverse events. 
10.8.5.2.2. Recording Adverse Events  
The adverse event reporting period for safety surveillance begins when the subject is initially 
included in the study (date of first signature of informed consent) and continues up to 30 days 
after the last study treatment administration. If an adverse event is not resolved or stabilized by 
this time, the Sponsor in consultation with the Investigator will decide whether to continue to 
monitor the adverse event or closeout the event in the database if no further follow-up is 
necessary. 
Any SAE suspected to be related to the study treatment must be reported whenever it occurs, 
irrespective of the time elapsed since the last administration. 
Investigator and study personnel will record all adverse events and SAEs whether received 
through an unsolicited report by a subject, elicited during subject questioning, discovered during 
physical examination, laboratory testing, and/or other means by recording them on the eCRF and 
SAE Report Form, as appropriate. The following information should be recorded on the adverse 
event eCRF: 
• Description including onset and resolution dates 
• Whether it met SAE criteria 
• Severity 
• Relationship to study treatment or other causality 
• Outcome 
For SAEs, events occurring secondary to the primary event should be described on the SAE 
Report Form in the narrative description of the case. 
The following should be considered when recording SAEs: 
• Death is an outcome of an event. The event that resulted in the death should be 
recorded and reported on both the SAE Report Form and eCRF. 
• For hospitalizations, surgical, or diagnostic procedures, the illness leading to the 
surgical or diagnostic procedure should be recorded as the SAE, not the procedure 
itself. The procedure should be captured in the narrative as part of the action taken in 
response to the illness. 
10.8.5.2.3. Diagnosis Versus Signs or Symptoms  
In general, the use of a unifying diagnosis is preferred to the listing out of individual symptoms. 
Grouping of symptoms into a diagnosis should only be done if each component sign and/or 
symptom is a medically confirmed component of a diagnosis as evidenced by standard medical 


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textbooks. If any aspect of a sign or symptom does not fit into a classic pattern of the diagnosis, 
report the individual symptom as a separate adverse event. 
10.8.5.3. Reporting Serious Adverse Events  
All SAEs are subject to reporting requirements.  
10.8.5.3.1. Serious Adverse Events  
All SAEs, whether or not considered related to study treatment, must be reported to the Sponsor 
Contact within 24 hours of becoming aware of the event. In addition, a completed report using 
the Sponsor’s SAE Report Form must be submitted within 24 hours of notification to the 
designated Sponsor Contact.  
IQVIA Pharmacovigilance 
Phone: +1-866-599-1341 
Fax: +1-866-599-1342 
Email (preferred method): ArenaSafety@iqvia.com 
If additional follow-up information is required or becomes available for a previously reported 
SAE, the new information should be reported to the designated Sponsor Contact within 24 hours 
of awareness. 
Elective hospitalization and/or surgery for clearly preexisting conditions (eg, a surgery that has 
been scheduled prior to the subject’s entry into the study) will not be reported as an SAE. All 
other hospitalizations, including elective hospitalizations for any condition that was not 
preexisting, will be reported as an SAE. 
Any SAE that is ongoing when the subject completes the study or discontinues the study will be 
followed by the Investigator until the event resolves, stabilizes or returns to Baseline status. 
10.8.5.3.2. Serious, Unexpected Adverse Drug Reactions  
All ADRs that are both serious and unexpected are subject to expedited reporting to regulatory 
agencies and will be reported in accordance with Directive 2001.20/EC or as per national 
regulatory requirements in participating countries. An unexpected ADR is one for which the 
nature or severity is not consistent with information in the relevant source documents. 
The following documents or circumstances will be used (by the Sponsor) to determine whether 
an adverse event/ADR is expected: 
1. For a medicinal product not yet approved for marketing in a country, the Reference 
Safety Information (RSI) section of a company’s current edition of the IB will serve as 
the source document in that country. 
2. Reports that add significant information on specificity or severity of a known, already 
documented serious ADR constitute unexpected events. For example, an event more 
specific or more severe than described in the RSI in the IB would be considered 
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10.8.5.4. BARC Bleeding Criteria Assessment  
Based on mild bleeding observed with escalating doses of oral temanogrel when co-administered 
with aspirin and clopidogrel in healthy adult subjects during Phase 1 studies, administration of 
single doses of IV temanogrel with DAPT in this study may potentially increase the tendency of 
bleeding; therefore, the assessment of bleeding will be categorized by the Investigator (or 
qualified designee) using the BARC definition for bleeding (Mehran 2011) (Table 3). For any 
bleeding events that occur after discharge and before the Follow-Up phone contact, applicable 
corresponding medical records should be requested for review by the Investigator (or qualified 
designee). 
Table 3: 
BARC Definitions for Bleeding 
Type 
Definition 
Type 0 
No bleeding 
Type 1 
Bleeding that is not actionable and does not cause the patient to seek unscheduled performance of 
studies, hospitalization, or treatment by a healthcare professional; may include episodes leading to 
self-discontinuation of medical therapy by the patient without consulting a healthcare professional 
Type 2 
Any overt, actionable sign of hemorrhage (ie, more bleeding than would be expected for a clinical 
circumstance, including bleeding found by imaging alone) that does not fit the criteria for Type 3, 4, 
or 5 but does meet at least one of the following criteria: 
1. Requiring nonsurgical, medical intervention by a healthcare professional. 
2. Leading to hospitalization or increased level of care. 
3. Prompting evaluation. 
Type 3 
a. 
Overt bleeding plus hemoglobin drop of 3 to < 5 g/dLa (provided hemoglobin drop is 
related to bleed) Any transfusion with overt bleeding.  
b. Overt bleeding plus hemoglobin drop ≥ 5 g/dLa (provided hemoglobin drop is related to 
bleed). Cardiac tamponade bleeding requiring surgical intervention for control 
(excluding dental/nasal/skin/hemorrhoid). Bleeding requiring intravenous vasoactive 
agents. 
c. 
Intracranial hemorrhage (does not include microbleeds or hemorrhagic transformation, 
does include intraspinal). Subcategories confirmed by autopsy or imaging or lumbar 
puncture. Intraocular bleed compromising vision. 
Type 4 
CABG-related bleeding. Perioperative intracranial bleeding within 48 hours. Reoperation after 
closure of sternotomy for the purpose of controlling bleeding. Transfusion of ≥ 5 U whole blood or 
packed red blood cells within a 48-hour period.b Chest tube output ≥ 2 L within a 24-hour period.          
Type 5 
Fatal bleeding 
a. 
Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious. 
b. Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation. 
a Corrected for transfusion (1 U packed red blood cells or 1 unit whole blood = 1 g/dL hemoglobin). 
b Cell saver products are not counted. 
Note: CABG indicates coronary artery bypass graft. Platelet transfusions should be recorded and reported but are not included in 
these definitions until further information is obtained about the relationship to outcomes. If a CABG-related bleed is not 
adjudicated as at least a Type 3 severity event, it will be classified as not a bleeding event. If a bleeding event occurs with a clear 
temporal relationship to CABG (ie, within a 48-hour time frame) but does not meet Type 4 severity criteria, it will be classified 
as not a bleeding event. 


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10.8.6. 
Pregnancy  
Women of childbearing potential may not participate in this study. Details of all pregnancies that 
occur in female subjects and female partners of male subjects that begin between the study 
treatment administration and 90 days after treatment administration will be collected. 
Pregnancy (during maternal or paternal exposure to study treatment) does not meet the definition 
of an adverse event; however, to fulfill regulatory requirements, any pregnancy and/or pregnancy 
outcome should be reported via the Pregnancy Report Form to the designated Sponsor Contact 
within 24 hours of awareness. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs and should be reported as such even if 
outside the SAE reporting period. 
10.9. 
Order of Events and Priority for Timed Assessments  
Every effort should be made to perform procedures as closely as possible to the scheduled times 
indicated in the Schedule of Assessments (Appendix 1). 
On Day 1, the timing of events should first be determined by subject safety requirements and 
then by the scheduled times and sequential order of events as described in this protocol, giving 
consideration to appropriate posture conditions, practical restrictions, and the other procedures 
scheduled to be performed at the same timepoint. The preferred order of events in the Peri-PCI 
period is as follows:  
1. Diagnostic angiography including confirmation of lesion-related eligibility (not required 
if a diagnostic angiography obtained within 60 days prior to Day 1 confirms lesion 
characteristics) 
2. Randomization 
3. Baseline peripheral blood draw 
4. Baseline target vessel angiographic measures (not required to be repeated if completed 
during diagnostic angiography at Check-in; in cases when diagnostic angiography is not 
performed at Check-in, lesion and vessel characteristics should be assessed as part of 
Baseline target vessel angiographic measures assessment prior to administration of study 
treatment) 
5. Baseline coronary physiology indices (IMR, CFR, FFR; not required to be repeated if 
completed at Check-in for confirmation of suitability for PCI per institutional standards)  
6. Treatment administration  
7. Post-treatment / pre-PCI peripheral blood draw (collected 0-2 minutes after the end of the 
IV administration of randomized study treatment) 
8. Post-treatment / pre-PCI coronary physiology indices (IMR, CFR, FFR) 
9. PCI with predilation (if applicable) and stent deployment 
10. Post-PCI (within 15 minutes of the completion of the PCI procedure) coronary artery 
(coronary ostium and coronary artery distal to the lesion) blood sampling 


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11. Post-PCI (within 15 minutes of the completion of the PCI procedure) coronary 
physiology indices (IMR, CFR, FFR) 
12. Post-PCI (within 15 minutes of the completion of the PCI procedure) target vessel 
angiographic measures  
13. Post-PCI (within 15 minutes of the completion of the PCI procedure) peripheral blood 
draw 
Specific timing of the study activities listed above is not critical (unless specified) as long as 
activities are completed in the order specified.  
10.10. 
Safety-Related Stopping Criteria  
Throughout the study, any bleeding event reported as BARC 3c or greater will pause study 
enrollment and trigger an ad hoc DSMB meeting. Study enrollment will remain paused until the 
DSMB has made a recommendation as to whether or not the study can continue.  
10.11. 
DSMB Review: Safety-Related Dose Escalation (Stage A)/Dose 
Recommendation (Stage B) Criteria  
At the completion of each cohort in Stage A the DSMB will use the following safety-related 
criteria to preclude recommendation of further dose escalation in Stage A and use of an 
associated dose in Stage B: 
• Two or more SAEs or two or more BARC 3b or higher events assessed as related to 
active study treatment within a cohort.  
• Two or more subjects on active treatment within a cohort experience an increase in 
alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 × upper 
limit of normal (ULN), or alkaline phosphate (ALP) or total bilirubin ≥ 2 × ULN, 
following study treatment administration. For subjects with values ≥ 2 × ULN prior to 
dosing, a 100% increase from pre-dosing value meets the criterion.  
• Seizure assessed as related to study treatment in a subject who received active study 
treatment.  
In addition to the safety-related criteria listed above, the DSMB will review overall safety data of 
each cohort (including AEs, clinical laboratory, and vital sign data) when recommending dose 
escalation within Stage A and doses for Stage B (Section 11.11).  
10.12. 
Approximate Blood Volume  
During the study, blood will be drawn for various analytes and panels, including chemistry, 
hematology, coagulation, PK, PD (cardiac markers, inflammatory markers), and serotonin 
concentration assessments. The approximate amount of blood to be drawn over the course of the 
study for each subject is expected to be 175 mL. 
10.13. 
Procedures for Overdose  
Overdose is not expected as study treatment will be administered in a highly controlled 
environment by qualified designees at the study centers. The Sponsor does not recommend 


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specific treatment for an overdose; there is no known antidote to temanogrel. After an overdose 
or suspected overdose, subjects should be monitored for adverse events.  
If a subject receives a dose in excess of the instructed dose (eg, due to pharmacy error) and if 
symptoms are present, the Investigator or designee should contact the Medical Monitor 
immediately. In the absence of associated adverse events as assessed per the clinical judgement 
of the Investigator, no further action is required. 


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11. 
PLANNED STATISTICAL METHODS  
11.1. 
General Considerations  
Details regarding the statistical analyses will be provided in a Statistical Analysis Plan (SAP), 
which will be finalized prior to study database lock (unblinding). 
Continuous variables will be summarized using the number of observations (n), mean, standard 
deviation (SD), median, minimum, and maximum. Categorical variables will be summarized 
using frequency counts and percentages.  
Unless otherwise specified, continuous endpoints will be analyzed using analysis of covariance 
(ANCOVA) with a model that includes treatment group and randomization stratification factor 
as factors and Baseline IMR value and Baseline value as covariates. Least square means, 
standard errors (SEs), and 95% confidence intervals (CIs) for the treatments and their difference 
will be presented together with their p-value. 
Proportion-based endpoints will be analyzed by either the Cochran-Mantel-Haenszel method 
adjusting for randomization stratification factor. The number and percentage of subjects 
achieving the goal and the difference in proportion between treatment groups achieving the goal, 
along with p-value and the 95% CIs will be reported. The odds ratio relative to placebo and 
percentage of difference from placebo will be presented together with corresponding 95% CIs 
and the p-value. 
Pairwise comparisons of each temanogrel treatment group compared to placebo will be 
conducted. In addition, analyses of the pooled temanogrel treatment groups compared to placebo 
will be conducted. 
Where statistical assumptions (eg, normality, proportional odds) are not met, alternative 
approaches will be evaluated (eg, non-parametric analysis, log transformation). 
Efficacy data will be analyzed by randomized treatment, while safety data will be analyzed by 
actual treatment received. 
All secondary and exploratory analyses will be interpreted in an exploratory manner. 
11.2. 
Determination of Sample Size  
This study is planned to randomize, treat, and complete safety, tolerability, PK, and PD 
assessments in approximately 99 subjects (12 in Stage A, 87 in Stage B). 
It is assumed that the primary endpoint, which is the change from Baseline in IMR measured 
immediately after PCI, is normally distributed with a mean of 6 and SD of 3.5. Assuming a 1:1:1 
randomization, 90 evaluable subjects (30 subjects in each of the 2 temanogrel treatment groups 
and placebo) is sufficient to achieve at least 90% power to detect a treatment effect of 3 (a 
clinically significant reduction of 50% from placebo) between each of the temanogrel treatment 
groups and placebo by a 2-sample t-test using a 2-sided significance level of 0.05. 
The primary endpoint analysis will be based on pooled data from subjects in Stage A and 
Stage B. 


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11.3. 
Analysis Sets  
For purposes of analysis, analysis sets are defined in Table 4. 
Table 4: 
Analysis Sets 
Analysis Set 
Description 
Full Analysis Set (FAS) 
The FAS will include all randomized subjects, irrespective of whether they 
received any study treatment. 
Modified Full Analysis Set 
(mFAS) 
The mFAS will include all subjects in the FAS who receive any study 
treatment and have at least a Baseline and Post-PCI IMR measurement. 
Per Protocol Set 
The Per Protocol Set will include all subjects in the FAS who receive the full 
dose of study treatment, have a Baseline and Post-PCI IMR measurement, and 
are without major protocol violations that might affect the evaluation of the 
effect of study treatment on the primary endpoint, which will be defined in the 
SAP.  
Pharmacokinetic Set 
The Pharmacokinetic Set will include all subjects in the Safety Set with at 
least 1 postdose PK measurement. 
Safety Set 
The Safety Set will include all subjects in the FAS who receive any study 
treatment. 
11.4. 
Missing Data  
Due to the trial design and short study duration, minimal missing data is expected. As a result, no 
algorithm for missing data imputation will be employed. 
11.5. 
Efficacy Analyses  
The primary and secondary endpoints will be analyzed using the Full Analysis Set (FAS). Other 
important statistical considerations such as sensitivity analyses and subgroup analyses will be 
described in the SAP. 
The primary endpoint of the study is the change from Baseline in IMR measured immediately 
after PCI. The primary PD analysis will be analyzed using ANCOVA with a model that includes 
treatment group and randomization stratification factor as factors and Baseline IMR as a 
covariate. Least square means, standard errors (SEs), and 95% CIs for the treatments and their 
difference will be presented together with their p-values. 
11.6. 
Study Endpoints  
The following definitions will be used to assess efficacy outcomes: 
11.6.1. 
Primary Endpoint  
• Change in IMR from Baseline to Post-PCI  
11.6.2. 
Secondary Endpoints  
• Change from Baseline to Post-PCI for the following assessments:  
− Coronary physiology indices (CFR, FFR) 


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− Angiographic measures (cTFC, TFG, TMPG) 
− Myocardial injury markers (CK, CK-MB, cTn) 
Note: Post-PCI measure for CK, CK-MB, and cTn, is collected 4 to 6 hours after 
completion of the PCI procedure and not immediately after completion of the 
procedure. 
• The incidence of procedural myocardial injury defined as: Elevation of cTn values 
> 99th percentile upper reference limit (URL) in subjects with normal Baseline values 
(≤ 99th percentile URL) or elevation of cTn by > 20% of the Baseline value in 
subjects with elevated cTn levels (> 99th percentile URL) 
• Concentration of temanogrel and active metabolites AR295980 and AR295981 prior 
to PCI and at selected post-PCI timepoints until discharge 
• Safety and tolerability of temanogrel 
11.6.3. 
Exploratory Endpoints  
• The relationship between temanogrel/active metabolite exposure and change in IMR 
from Baseline to Post-PCI (and potentially other PD assessments) 
• The relationship between coronary physiology indices/angiographic measures and 
peripheral serotonin concentrations at Baseline and Post-PCI 
• The relationship between coronary physiology indices/angiographic measures and 
coronary artery serotonin concentration (obtained on blood samples drawn from the 
coronary ostium and from coronary artery distal to the lesion) Post-PCI 
• The relationship between the level of P2Y12 platelet inhibition and peripheral/ 
coronary artery (obtained on blood samples drawn from the coronary ostium and from 
coronary artery distal to the lesion) serotonin concentrations  
• Change in IMR (and potentially other coronary physiology indices) from Baseline to 
Pre-PCI  
• Change in QCA from Baseline to Post-PCI  
• Change in the following markers of inflammation from Baseline to post-procedure: 
− hs-CRP, PTX-3 
− Cytokines (IL-1, IL-6, IL-8, IL-10, and TNF-α) 
11.6.4. 
Pharmacokinetic Analysis  
The PK analysis will be conducted using model independent methods and based on plasma 
concentrations of temanogrel and its metabolites from subjects who have received temanogrel. 
Cmax and potentially additional pharmacokinetic parameters, will be derived from subjects with 
evaluable plasma concentration versus time profiles. 
Individual plasma concentrations of temanogrel and metabolites will be listed for each subject 
using the actual sampling time and dose level. The Pharmacokinetic Set will be used to analyze 
plasma concentrations. Mean, SD, CV (%), median, minimum, and maximum values will be 


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summarized descriptively as appropriate per dose level. Individual subject plasma concentration 
versus time profiles of temanogrel and its metabolites will be plotted on both a linear and a 
semilogarithmic scale for each dose level. Mean values, as appropriate, will also be presented 
graphically for each dose level. 
Detailed PK analysis procedures of temanogrel and its metabolites will be provided in the SAP. 
11.6.5. 
Pharmacokinetic/Pharmacodynamic Relationship  
Relationships will be explored between selected plasma exposure measures (to be determined) of 
selected analytes (temanogrel, its active metabolites, and/or all analytes combined) and selected 
PD measures (eg, change from Baseline to Post-PCI in IMR and/or other cardiac physiology 
indices, angiographic measures, markers of myocardial injury/infarction, or markers of 
inflammation). 
Detailed description of the exploratory PK/PD analyses will be provided in the SAP. 
11.7. 
Subgroup Analysis  
• Sex (male, female) 
• Race (white, non-white) 
• Age (≤ or > median) 
• Baseline IMR (≤ or > median) 
• Subject type (elective PCI or PCI for NSTEMI/UA) 
• Lesion length (≤ or > median) 
• P2Y12 inhibitor exposure (ticagrelor, prasugrel, clopidogrel) 
• Time of P2Y12 administration (long-term or procedure loading dose) 
Details of the subgroup analyses will be provided in the SAP. 
11.8. 
Testing Strategy  
Since this is an exploratory proof of concept study, no formal testing strategy or adjustments of 
the Type I error will be employed for the evaluation of secondary or exploratory endpoints. 
Estimates and CIs for treatment groups and from pairwise comparisons will be reported in an 
exploratory manner. 
11.9. 
Interim Analysis  
No formal interim analysis of efficacy is planned. 
11.10. 
Safety Analyses  
Adverse events will be listed and summarized by system organ class and preferred term, as well 
as according to severity and causality/relationship to temanogrel. Treatment-emergent adverse 
events (TEAEs) will be summarized by stage, cohort, and treatment group. In addition, TEAEs 
will be pooled across treatment groups (ie, placebo, temanogrel). Similarly, bleeding events will 


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be summarized by BARC classification by stage, cohort, and treatment group and pooled across 
treatment groups. Observed values for clinical laboratory tests, vital signs, and safety 12-lead 
ECGs, will be summarized by stage, cohort, treatment group, and timepoint. Individual data 
listings of clinical laboratory tests results will be presented for each subject. Observed values and 
changes from Baseline will be summarized descriptively. Safety 12-lead ECG data (observed 
values and change from Baseline) will be listed for each subject and timepoint. Observed values 
will be classified for normal, abnormality that is not clinically significant, and clinically 
significant abnormality by stage, cohort, treatment group, and timepoint of collection. Results of 
other safety assessments will be listed and summarized as appropriate. 
A detailed description of all safety analyses will be provided in the SAP. 
11.10.1. 
Safety Endpoints  
The safety endpoints will be analyzed using the Safety Set. The primary safety endpoint of the 
study is the assessment of TEAEs. All bleeding-related adverse events will be classified using 
the BARC criteria. 
• Incidence of all TEAEs 
• Incidence of TEAEs by severity 
• Incidence treatment-related TEAEs 
• Incidence of bleeding-related TEAEs classified using BARC criteria 
• Incidence of adverse events leading to discontinuation (if any) 
• Incidence of SAEs (if any) 
• Incidence and severity of laboratory abnormalities, and change from Baseline in 
laboratory values (to include hematology, serum chemistry, and coagulation)  
• Incidence of clinically significant vital sign abnormalities and changes from Baseline 
• Incidence of clinically significant ECG abnormalities and changes from Baseline 
11.10.2. 
Adverse Events  
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). 
For each treatment group, the proportion of subjects with treatment emergent adverse events will 
be summarized overall, by severity, and by relationship to study treatment. SAEs will also be 
summarized by treatment group. A treatment emergent adverse event is defined as: 
• An adverse event that occurs after initiation of study treatment that was not present at 
the time of treatment start. 
• An adverse event that increases in severity after the initiation of medication, if the 
event was present at the time of treatment start. 
Adverse events occurring before the first dose of study treatment will be summarized separately. 


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11.10.3. 
Clinical Laboratory Parameters  
Clinical laboratory parameters will be summarized by treatment group at each scheduled 
assessment timepoint using descriptive statistics. 
In the event of abnormal clinical laboratory values, the Investigator will make a judgment 
whether or not the abnormality is clinically significant. Clinically significant abnormal values 
should be reported as adverse events as described in Section 10.8.5.2. 
11.10.4. 
Electrocardiograms  
The Investigator is responsible for interpretation of ECG data for eligibility purposes and safety 
monitoring. ECG data will also be read and interpreted by a central ECG lab. Individual ECG 
values will be listed by timepoint and summarized using descriptive statistics. Parameters to be 
provided for each ECG are: HR, RR, PR, QRS, QT, QTc, QTcB, and QTcF. Post-Baseline ECGs 
for each subject will be compared with the Baseline ECG. Any clinically significant change from 
Baseline may be recorded as an adverse event if deemed appropriate by the Investigator, or 
Investigator in consultation with the Clinical Lead. Outlier analysis will be performed on all 
subjects with QTcF values greater than 500 ms or change from Baseline > 60 ms in the absence 
of Baseline ECG abnormalities that preclude accurate surface ECG assessment of ventricular 
repolarization (eg, bundle branch block). 
ECG monitoring during catheterization procedures will occur per site standard of care and any 
clinically significant findings will be recorded as adverse events in the eCRF. 
11.10.5. 
Vital Signs  
Vital signs measurements will include blood pressure, heart rate, respiratory rate, and 
temperature. Vital signs values collected at Screening, Check-in, and prior to discharge will be 
recorded in the eCRF.  
Vital signs monitoring during catheterization procedures will be conducted per site standard of 
care and any clinically significant findings will be recorded as adverse events in the eCRF. 
11.10.6. 
Physical Examination  
Clinically significant physical examination abnormalities will be included in the medical history 
or recorded and summarized as an adverse event. 
11.11. 
Data and Safety Monitoring Board  
An independent DSMB will be established for the regular and ad hoc review of safety data. 
Membership of the DSMB, meeting frequency, and safety review criteria are defined in a 
separate DSMB charter. The DSMB will review unblinded safety data at each meeting. At the 
conclusion of each meeting, the DSMB will provide a recommendation to the Sponsor Liaison. 
During Stage A, the DSMB will review unblinded safety data at the completion of each cohort. 
At the conclusion of the first cohort in Stage A, taking into account safety-related dose escalation 
stopping criteria (Section 10.11), and in consideration of other AEs, laboratory, and vital sign 
data, the DSMB will provide a recommendation as to whether or not dose escalation to the next 
planned dose level in Stage A should occur; the DSMB may also recommend evaluation of an 


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alternative dose in the second cohort in Stage A. At the conclusion of the second dose cohort in 
Stage A, the same criteria will be used by the DSMB to provide a recommendation as to whether 
or not the study should proceed with Stage B; the DSMB may recommend evaluation of an 
alternative dose (not to exceed the maximum planned dose of 40 mg) in an additional third dose 
cohort in Stage A prior to progression to Stage B. At the conclusion of the final cohort in 
Stage A, the DSMB will provide recommendation on temanogrel doses to be evaluated in 
Stage B, based on safety and tolerability data in Stage A. 
During Stage B, the DSMB will conduct safety data reviews at specified intervals in accordance 
with the DSMB Charter.  
Throughout the study, any bleeding event reported as BARC 3c or greater will pause study 
enrollment and trigger an ad hoc DSMB meeting (Section 10.10). Study enrollment will remain 
paused until the DSMB has made a recommendation as to whether or not the study can continue.  
To ensure the scientific integrity of the study, members of the DSMB will not be directly 
involved in the ongoing management of the study. 
In addition to members of the DSMB, an independent statistician responsible for interacting with 
the DSMB will have access to unblinded study data. This statistician will not be directly 
involved in the conduct of the study. 


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12. 
ETHICAL CONSIDERATIONS  
12.1. 
Ethical Conduct of the Study  
This study shall be conducted in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki and that are consistent with GCP, ICH guidelines, and other 
applicable regulatory requirements (eg, local requirements). 
12.2. 
Institutional Review Board or Independent Ethics Committee 
Approval  
Before initiating a study, the Investigator must have written and dated approval from the 
IRB/IEC for the study protocol, written informed consent form (ICF), subject recruitment 
materials and procedures (eg, advertisements or websites), and any other written information to 
be provided to subjects. Approval from the committee must be documented in a letter to the 
Investigator specifying the protocol number, protocol version, documents reviewed, and the date 
on which the committee met and granted the approval. 
All documents subject to review during the study, including any modifications made to the 
protocol after receipt of IRB/IEC approval, must also be submitted to the committee for approval 
prior to implementation. The Investigator must also provide periodic reports as required and 
promptly report important safety information (ie, SAEs) and protocol violations, as appropriate, 
to the IRB/IEC. 
As part of the Investigator’s written application to the IRB/IEC, the Investigator should provide 
the committee with a current copy of the IB. If the IB is updated during the study, the 
Investigator should supply an updated copy to the committee. 
12.3. 
Informed Consent  
The Investigator will fully inform the subject of all pertinent aspects of the study, including the 
approval of the study by the IRB/IEC. Before informed consent may be obtained, the 
Investigator should provide the subject ample time and opportunity to inquire about details of the 
study and to decide whether to participate. 
Prior to a subject’s participation in the study, the IRB/IEC-approved ICF must be signed and 
personally dated by the subject and by the person who conducted the informed consent 
discussion. If a subject is unable to read, an impartial witness will be present during the entire 
informed consent discussion and will sign the informed consent form. 
The written ICF and any other written information to be provided to subjects should be revised 
whenever important new information becomes available that may be relevant to the subject’s 
consent. Any revised written ICF or study materials to be available and/or supplied to subjects 
should receive the IRB/IEC’s approval in advance of use. Revised ICFs require subjects to 
reconsent, sign, and date the new ICF. The subject will be informed in a timely manner if new 
information becomes available that may be relevant to the subject’s willingness to continue 
participation in the study. The communication of this information should be documented. 


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12.4. 
Confidentiality  
All information generated in this study is considered highly confidential and must not be 
disclosed to any person or entity not directly involved with the study unless prior written consent 
is provided from the Sponsor. 
Prior to study participation, the Investigator shall inform the subject that the monitor(s), 
auditor(s), IRB/IEC, and the regulatory authorities will be granted direct access to the subject’s 
original medical records for verification of clinical study procedures and/or data, and that, by 
signing a written ICF, the subject is authorizing such access. 
In addition, prior to study participation, the subject must be informed that the records identifying 
the subject will not be made publicly available; if the results of the study are published, the 
subject’s identity will remain confidential. 
12.5. 
Protocol Compliance  
The Investigator/institution will conduct the study in compliance with the protocol agreed to by 
the Sponsor and regulatory authorities (if applicable) and that was approved by the IRB/IEC. The 
Investigator/institution and the Sponsor should sign the protocol, or an alternative contract, to 
confirm agreement. 
The Investigator should not implement any deviation from, or changes to, the protocol without 
agreement by the Sponsor and prior review and documented approval from the IRB/IEC of an 
amendment, except where necessary to eliminate immediate hazard(s) to study subjects or when 
the change involves only logistical or administrative aspects of the study (eg, change in monitor, 
change of phone number). 
When an important deviation from the protocol is deemed necessary for an individual subject, 
the Investigator must contact the Medical Monitor for the study. Such contact must be made as 
soon as possible to permit a review by the Sponsor to determine the impact of the deviation on 
the subject’s participation and/or the assessment of safety or other outcomes in the study. Any 
significant protocol deviations affecting subject eligibility and/or safety must be reported by 
Investigator or site delegate to the IRB/IEC and regulatory authorities, as applicable, prior to 
implementation. 
The Investigator should document and explain any deviation from the approved protocol. 


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13. 
QUALITY CONTROL AND QUALITY ASSURANCE  
Quality assurance and quality control systems shall be implemented and maintained with written 
SOPs to ensure that the study is conducted and data are generated, documented (recorded), and 
reported in compliance with the protocol, GCP, and the applicable regulatory requirement(s). 
Quality control shall be applied to each stage of data handling to ensure that all data are reliable 
and have been processed correctly. 
An agreement must be secured from all involved parties to ensure direct access to all 
study-related sites, source documents, and reports for the purpose of monitoring and auditing by 
the Sponsor and inspection by regulatory authorities. 
13.1. 
Training of Study Site Personnel  
Prior to study activities being initiated at the study site, the Sponsor or designee will train study 
site personnel on the protocol and applicable procedures. Training should be documented. 
If new study site personnel are assigned to the study after the initial training, study sites should 
contact the study monitor to coordinate training. Qualified study personnel may conduct training, 
as appropriate, if deemed acceptable by the monitor and Sponsor. Training of new study 
personnel should also be documented. 
13.2. 
Monitoring  
Study site monitoring is conducted to ensure the study is progressing as expected, the rights and 
well-being of human subjects are protected, the reported study data are accurate, complete, and 
verifiable, and the conduct of the study is in compliance with the currently approved protocol, 
with GCP and with applicable regulatory requirements. Protocol deviations identified will be 
documented.  
Details of study site monitoring are documented in the study Clinical Monitoring Plan (CMP) or 
similar document. The CMP describes in detail who will conduct the monitoring, at what 
frequency monitoring will be done, at what level of detail monitoring will be performed (eg, 
targeted and/or risk based), and the distribution of monitoring reports. Monitoring may include a 
study site selection visit, which may be conducted in person or via communication media (eg, 
teleconference, online meeting) or may be waived in accordance with policy and procedures 
being followed for the study, if appropriate. Monitoring will include a study site initiation visit, 
interim monitoring visit(s), and a study site closeout visit. An interim monitoring visit may be 
combined with a closeout visit, if applicable. 
13.3. 
Audit  
An audit of one or more participating study sites may be performed independently of, and 
separately from, routine monitoring to evaluate clinical study conduct and compliance with the 
protocol, SOPs, GCP, and the applicable regulatory requirements. 


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14. 
DATA HANDLING AND RECORD KEEPING  
14.1. 
Data Management  
14.1.1. 
Case Report Forms  
An eCRF must be completed for each subject screened/enrolled in this study. These forms will 
be used to transmit information collected during the study to the Sponsor and regulatory 
authorities, as applicable. 
The documentation related to the validation of the eCRFs will be maintained in the Trial Master 
File (TMF). The TMF will be maintained by the clinical research organization and will be 
archived by the Sponsor. 
The Investigator will document subject data in his/her own subject files. These subject files will 
serve as source data for the study. All eCRF data required by this protocol will be recorded by 
study site personnel. All data entered into the eCRF will be supported by source documentation. 
The Investigator or an authorized member of the Investigator’s staff will make any necessary 
corrections to the eCRF. All changed information, including the date and person performing the 
corrections, will be available via the audit trail, which will be part of the electronic data capture 
system. For any correction, a reason for the alteration will be provided. The eCRFs will be 
reviewed periodically for completeness and acceptability by Sponsor personnel (or their 
representatives). The Sponsor (or their representatives) will also be allowed access to all source 
documents pertinent to the study in order to verify eCRF entries. The Investigator will review the 
eCRFs for completeness and accuracy and provide his or her electronic signature and date to the 
eCRFs as evidence thereof. 
14.1.2. 
Source Documents  
Per regulatory requirements, the Investigator or designee will maintain accurate and up-to-date 
study documentation, including source documentation for each study subject. Source documents 
are defined as original documents, data, and records. These may include, but are not limited to, 
hospital records, clinical and office charts, laboratory data/information, evaluation checklists, 
pharmacy dispensing and other records, recorded data from automated instruments, ECGs, 
X-rays, ultrasounds, right heart catheterization reports, or echocardiograms. Data collected 
during this study must be recorded on the appropriate source documents. 
The Investigator(s)/institution(s) will permit study-related monitoring, audits, IRB/IEC review, 
and regulatory inspection(s) and will provide direct access to the source data. 
14.2. 
Study Documentation and Records Retention  
The Investigator and study staff have the responsibility of maintaining a comprehensive and 
centralized filing system containing all study-related documentation. These files must be 
available for inspection by the Sponsor, representatives of the Sponsor, the IRB/IEC, and 
regulatory authorities (ie, FDA or international regulatory authorities) at any time, and should 
consist of the following elements: 


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• Subject files containing the completed eCRFs (if applicable), supporting source 
documentation including medical records, laboratory data, and signed ICFs. 
• Regulatory files containing the protocol with all amendments and Investigator 
signature pages, copies of all other regulatory documentation, all correspondence 
between the study site and the IRB/IEC and Sponsor, and drug accountability files, 
including a complete account of the receipt and disposition of the study treatment. 
Records will be available for 2 years after the last marketing application approval, or if the 
application is not approved or never submitted, 2 years after the appropriate regulatory 
authorities have been notified of the discontinuation of clinical development of the 
investigational product. After the 2 years period has elapsed, the site will contact the Sponsor to 
inquire about the desired sponsor-approved destination for the study documents. Shipment of the 
appropriate study files will be arranged by the sponsor and site. 
During the record retention period, the Investigator or designee must inform the Sponsor or 
designee (eg, CRO), of the following: 
• Location of study documentation 
• If the Investigator is unable to retain documentation for the specified period 
14.3. 
Clinical Study Report  
Whether the study is completed or prematurely terminated, a clinical study report will be 
prepared and provided to the regulatory agencies according to applicable regulatory 
requirement(s). 
14.4. 
Disclosure of Study Results  
The Sponsor will post the results of the study in a publicly accessible database in accordance 
with the applicable laws and regulations. 


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15. 
RESPONSIBILITIES  
15.1. 
Investigator Responsibilities  
The Investigator must comply with this protocol and the conduct of all study procedures. The 
Investigator will disclose to the Sponsor sufficient, accurate, financial information to allow the 
Sponsor to submit accurate disclosure statements to the FDA per 21 Code of Federal Regulations 
Part 54 (Financial Disclosure by Clinical Investigators) or to other regulatory authorities that 
have similar requirements. The Investigator is responsible for compliance with applicable 
sections of ICH GCP requirements. The investigator may also be responsible for compliance 
with 21 Code of Federal Regulations Part 312, Subpart D (Responsibilities of Investigators) and 
other, federal, and local laws, applicable to conducting drug studies. 
The Investigator is responsible for ensuring an investigation is conducted according to the signed 
Investigator statement, the investigational plan, and applicable regulations; for protecting the 
rights, safety, and welfare of subjects under the Investigator’s care; and for the control of drugs 
under investigation. An Investigator shall, in accordance with the provisions of ICH GCP 
guidelines and/or 21 Code of Federal Regulations Part 50, obtain the informed consent of each 
human subject to whom the drug is administered. 
15.2. 
Sponsor Responsibilities  
The Sponsor is responsible for compliance with applicable sections of ICH E6(R2) and 21 Code 
of Federal Regulations Part 312, Subpart D (Responsibilities of Sponsors). The Sponsor is 
responsible for selecting qualified Investigators, providing them with the information they need 
to conduct an investigation properly, and ensuring proper monitoring of the investigation(s), 
ensuring the investigation(s). Sponsors are also responsible for ensuring the investigation(s) is 
conducted in accordance with the general investigational plan and protocols contained in the 
Investigational New Drug (IND) application (or equivalent), maintaining an effective IND (or 
equivalent) with respect to the investigations, and ensuring the FDA (and/or other regulatory 
authorities as applicable), and all participating Investigators are promptly informed of significant 
new adverse effects or risks with respect to the drug. 


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TIMIStudyGroup. The thrombolysis in myocardial infarction (TIMI) trial. Phase I findings. N 
Engl J Med. 1985;312(14):932-936.  
Van Assche LMR, Bekkers SCAM, Senthilkumar A, Parker MA, Kim HW, Kim RJ. The 
prevalence of microvascular obstruction in acute myocardial infarction: Importance of ST 
elevation, infarct size, transmurality and infarct age. J Cardiovasc Magn Reson. 2011;13(Suppl 
1):P147.  


Clinical Study Protocol 
 
APD791-202 
Temanogrel in PCI 
 
Amendment 3.0 
Arena Pharmaceuticals, Inc. 
Confidential 
Page 78 of 83 
van den Berg EK, Schmitz JM, Benedict CR, Malloy CR, Willerson JT, Dehmer GJ. 
Transcardiac serotonin concentration is increased in selected patients with limiting angina and 
complex coronary lesion morphology. Circulation. 1989;79(1):116-124.  
van Kranenburg M, Magro M, Thiele H, et al. Prognostic value of microvascular obstruction and 
infarct size, as measured by CMR in STEMI patients. JACC Cardiovasc Imaging. 
2014;7(9):930-939.  
Vikenes K, Farstad M, Nordrehaug JE. Serotonin is associated with coronary artery disease and 
cardiac events. Circulation. 1999;100(5):483-489.  
Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute 
coronary syndromes. N Engl J Med. 2009;361(11):1045-1057.  
WHO. Cardiovascular diseases (CVDs). World Health Organization. https://www.who.int/news-
room/fact-sheets/detail/cardiovascular-diseases-(cvds). Published 2017. Updated May 17, 2017. 
Accessed June 28, 2018. 
Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute 
coronary syndromes. N Engl J Med. 2007;357(20):2001-2015.  
Wright L, Homans DC, Laxson DD, Dai XZ, Bache RJ. Effect of serotonin and thromboxane A2 
on blood flow through moderately well developed coronary collateral vessels. J Am Coll 
Cardiol. 1992;19(3):687-693.  
Yong AS, Layland J, Fearon WF, et al. Calculation of the index of microcirculatory resistance 
without coronary wedge pressure measurement in the presence of epicardial stenosis. JACC 
Cardiovasc Interv. 2013;6(1):53-58.  
Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with 
acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345(7):494-502.  
 
 


Clinical Study Protocol 
 
APD791-202 
Temanogrel in PCI 
 
Amendment 3.0 
Arena Pharmaceuticals, Inc. 
Confidential 
Page 79 of 83 
APPENDIX 1: 
SCHEDULE OF ASSESSMENTS  
Timepoint 
 
 
Peri-PCI 
Post-PCI 
Screening 
Check-ina             
Baselineb 
Dosing 
Pre-PCI 
Post-PCIc 
6 h (± 2 h) 
Post-PCId 
24 h (± 2 h) 
Post-
Procedure/ 
Dischargee 
Follow-Up  
Phone Callf 
Study Day 
−14 to 1 
1 
1 
1 or 2 
8 (± 2 Days) 
Informed consent 
X 
Inclusion/exclusion 
X 
X 
Demographics 
X 
Medical history 
X 
X 
Physical examinationg                  
X 
 
 
 
 
 
 
X 
 
Prior/concomitant medications 
 
Height 
X 
Body weight 
X 
X 
 
 
 
 
 
 
 
Clinical chemistry and hematologyh                  
X 
X 
X 
Selected clinical chemistry/hematology Check-in 
assessmentsh 
 
X 
 
 
 
 
 
 
 
Coagulation panelh 
 
 
X 
 
 
X 
X 
X 
 
Urine drug screenh 
 
X 
 


Clinical Study Protocol 
 
APD791-202 
Temanogrel in PCI 
 
Amendment 3.0 
Arena Pharmaceuticals, Inc. 
Confidential 
Page 80 of 83 
Timepoint 
 
 
Peri-PCI 
Post-PCI 
Screening 
Check-ina             
Baselineb 
Dosing 
Pre-PCI 
Post-PCIc 
6 h (± 2 h) 
Post-PCId 
24 h (± 2 h) 
Post-
Procedure/ 
Dischargee 
Follow-Up  
Phone Callf 
Study Day 
−14 to 1 
1 
1 
1 or 2 
8 (± 2 Days) 
ECGi                  
X 
Xj 
X 
Blood pressure and heart ratek                  
X 
X 
X 
Respiratory rate and body temperature 
 
X 
 
 
 
 
 
X 
 
Adverse event reporting 
 
Randomization 
Xl          
Study treatment administration 
X 
P2Y12 VerifyNow 
 
 
X 
 
 
X 
 
 
 
Peripheral serotonin assessmentm                  
X 
X 
Coronary artery serotonin assessmentn                  
 
 
 
 
 
Xo 
 
 
 
Coronary physiology indicesp                  
X 
X 
Xo 
Markers of inflammationh     
X 
X 
X 
X 
Markers of myocardial injuryh      
X 
X 
X 
X 
Diagnostic angiography with confirmation of lesion 
characteristicsq                  
 
X 
 
 
 
 
 
 
 


Clinical Study Protocol 
 
APD791-202 
Temanogrel in PCI 
 
Amendment 3.0 
Arena Pharmaceuticals, Inc. 
Confidential 
Page 81 of 83 
Timepoint 
 
 
Peri-PCI 
Post-PCI 
Screening 
Check-ina             
Baselineb 
Dosing 
Pre-PCI 
Post-PCIc 
6 h (± 2 h) 
Post-PCId 
24 h (± 2 h) 
Post-
Procedure/ 
Dischargee 
Follow-Up  
Phone Callf 
Study Day 
−14 to 1 
1 
1 
1 or 2 
8 (± 2 Days) 
Assessment of target vessel angiographic measuresr             
X 
X 
PK blood draw 
X 
Xs        
X 
X 
Xt 
a Check-in assessments include pre-randomization confirmation of eligibility on Day 1. Screening assessments are not required to be repeated at Check-in for subjects for whom 
Screening occurs on the same day as Check-in (Day 1). 
b Baseline assessments are to occur after confirmation of eligibility/randomization and prior to study treatment administration. 
c Post-PCI assessments are to occur within 15 minutes of the completion of the PCI procedure. For ECG assessment, follow footnote “j” below.  
d If subjects are discharged less than 2 hours after the 6-hour Post-PCI assessments have been completed, any assessments scheduled for discharge must be performed, but 
assessments scheduled at both 6 hours Post-PCI and discharge do not need to be repeated. 
e Subjects will be discharged at the Investigator’s discretion based upon clinical presentation, but not prior to the collection of all 6-hour Post-PCI assessments. 
f Site staff will work with subjects who withdraw early to obtain as much follow-up data as possible. 
g A physical examination is performed per the site’s standard of care at Screening. A symptom-based physical exam is performed prior to discharge. 
h Refer to Table 2 for additional information.  
i ECG monitoring during catheterization procedures is to occur per site standard of care and any clinically significant findings will be recorded as adverse events in the eCRF. 
j To be collected after the completion of the PCI procedure and at least 1-hour postdose. 
k Blood pressure and heart rate monitoring during catheterization lab procedures will be conducted per site standard of care and any clinically significant findings will be recorded 
as adverse events in the eCRF. 
l Randomization is to occur after confirmation of all inclusion and exclusion criteria on Day 1. 
m Peripheral serotonin is assessed from a blood sample obtained by peripheral venipuncture or preferably using an indwelling catheter (central line can be used if available). 
n Coronary artery serotonin is assessed from blood samples obtained from the coronary ostium and from coronary artery distal to the lesion using an aspiration catheter. 
o To be performed as soon as possible after completion of the PCI procedure. 
p Coronary physiology indices include IMR, CFR, and FFR. Assessment of Baseline coronary physiology indices can be performed prior to randomization at Check-in for 
confirmation of suitability for PCI per institutional standards. 
q Confirmation of lesion and vessel characteristics is required for eligibility purposes prior to randomization. Diagnostic angiography including confirmation of lesion-related 
eligibility can be performed prior to randomization at Check-in or within 60 days prior to Day 1. In cases when diagnostic angiography is not performed at Check-in, lesion and 
vessel characteristics should be assessed as part of Baseline target vessel angiographic measures assessment prior to administration of study treatment. 
r Angiographic measures of target vessel include cTFC, TFG, TMPG, QCA, and assessment of lesion and vessel characteristics. Assessment of Baseline target vessel angiographic 
measures can be performed during diagnostic angiography at Check-in. 
s To occur 0-2 minutes after the IV administration of study treatment has been completed and prior to coronary physiology measurements.  
t The final PK blood draw is to occur at 24 hours post-PCI or at discharge, whichever occurs first.  


Clinical Study Protocol 
 
APD791-202 
Temanogrel in PCI 
 
Amendment 3.0 
Arena Pharmaceuticals, Inc. 
Confidential 
Page 82 of 83 
CFR, coronary flow reserve; eCRF, electronic case report form; cTFC, corrected TIMI frame count; ECG, electrocardiogram; FFR, fractional flow reserve; h, hour; IMR, index of 
microcirculatory resistance; IV, intravenous; PCI, percutaneous coronary intervention; PK, pharmacokinetic; QCA, quantitative coronary analysis; TFG, TIMI flow grade; TIMI, 
thrombolysis in myocardial infarction; TMPG, thrombolysis in myocardial infarction myocardial perfusion grade 
 


Clinical Study Protocol 
 
APD791-202 
Temanogrel in PCI 
 
Amendment 3.0 
Arena Pharmaceuticals, Inc. 
Confidential 
Page 83 of 83 
APPENDIX 2: 
INVESTIGATOR SIGNATURE  
 
Study title: 
A Phase 2, Multicenter, Randomized, Double-Blind, 
Placebo-Controlled Study to Assess the Safety, Tolerability, and Effect 
on Microvascular Obstruction of Temanogrel in Subjects Undergoing 
Percutaneous Coronary Intervention 
Study number: 
APD791-202 
 
 
I have read the protocol described above. I agree to comply with all applicable regulations and to 
conduct the study as described in the protocol. 
 
 
 
 
 
 
 
 
Investigator Signature 
 
Date 
 
 
 
 
 
 
Investigator Name and Credentials - Printed 
 
 
 
 
 
 
 
 
Institution Name – Printed 
 
 
 
 
 
 
 
 
 
 
 


Na me: Cli nical St u d y Pr ot oc ol: A P D 7 9 1- 2 0 2 A me n d me nt 3. 0
Descri pti o n: A P hase 2, M ultice nter, Ra n d o mize d, D o u ble- Bli n d, Place b o- C o ntr olle
User Na m
Ca pacit y: 
Mea ni n g: A p pr o val Tas k
Date: 1 7- Ma y- 2 0 2 2 0 5: 3 8: 0 7 G M T + 0 0 0 0
P P D
P P D


A P D 7 9 1- 2 0 2- P h ar m ac oki n etic N T F, 0 9 D ec e m b er 2 0 2 2 
N ot e t o Fil e T e m pl at e V ersi o n 1. 0, 2 8 A u g 2 0 2 0 
 
P a g e 1  of 4                              
 
N ote t o Fil e, A d de n d u m 
 
 
D ate:  
0 9 Dece m ber 2 0 2 2 
T o:  
T M F 
Fr o m:   
 
 
 
 
 
 
Pr ot oc ol N o.:  
A P D 7 9 1- 2 0 2 
S u bject:   
D oc u me nt t he stat us of d oc u me nts a n d o utli ne pla ns f or sele ct p ost- data base l oc k 
p har mac o ki netic a nal yses 
 
B ac k gr o u n d: 
O n 2 5 A u g ust 2 0 2 2, t he decisi o n was ma de t o disc o nti n ue de vel o p me nt of t he 
Are na car di o vasc ular pr o gra ms, w hic h i ncl u des A P D 7 9 1. 
As a r es ult of t he i m me diate ter mi nati o n, t he bi ostatistics as pe cts relate d t o 
fi nalizi n g d oc u me nts (e. g., statistic al a nal ysis pla n [ S A P]) a n d ot her d o w nstrea m 
a cti vities pertai ni n g t o p har mac o ki netic a nal yses were eit her i m mat ure a n d/ or ha d 
n ot be e n esta blis he d. T hese tas ks w o ul d ha ve ta ke n si g nific a nt ti me a n d res o urces 
b y b ot h t he Are na a n d Me d pace tea m t o fi nalize, w hic h was n ot feasi ble gi ve n t he 
a ccelerate d st u d y cl ose- o ut ti meli ne, i ncl u di n g t he data base l oc k ( D B L) w hic h 
occ urre d o n 1 0 Oct o ber 2 0 2 2. T he d oc u me nt here ser ves as t he a d de n d u m t o 
A P D 7 9 1- 2 0 2 N T F (a p pr o ve d o n 0 7 Oct o ber 2 0 2 2) t o o utli ne t he pla ns f or sele ct 
p ost- data base l oc k p har mac o ki netic a nal yses. 
Fi n al St at us:
 
P har mac o ki netic A nal ysis 
 
As per draft statistical a nal ysis pla n ( S A P) v 0. 3 
 
Fi nal p har mac o ki netic para meters recei ve d fr o m Me d pace o n D ec e m ber 5, 
2 0 2 2 
 
P har mac o ki netics- P har mac o d y na mics A nal ysis  
 
De vel o p me nt has n ot be g u n. 
 
S er ot o ni n A nal ysis
 
De vel o p me nt has n ot be g u n. 
 
Ra w data f or plas ma ser ot o ni n c o nce ntrati o ns were recei ve d o n 1 9 Oct o ber 
2 0 2 2 
 
D eliver a bles & 
A n alyses: 
P har mac o ki netic( P K)  para meters w ere esti mate d as per state d i n S A P ( v 0. 3) b y 
Me d pace Pers o n nel. T F Ls c o ntai ni n g ke y p har mac o ki netic i nf or mati o n w ere 
P P D
P P D


A P D 7 9 1- 2 0 2- P h ar m ac oki n etic N T F, 0 9 D ec e m b er 2 0 2 2
N ot e t o Fil e T e m pl at e V ersi o n 1. 0, 2 8 A u g 2 0 2 0
P a g e 2 of 4                              
pr o d uce d as prese nte d i n A p pe n di x A of t his N ote t o File, A d de n d u m. Are na 
utilize d t his e xisti n g r e p ort str uct ure i n place of S A P- base d T F Ls f or t he fi nal 
re p ort.
Si g n at ures:
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
Distri b uti o n:
  T M F or a p plica ble d oc u me nt re p osit or y
P P D
P P D
P P D
P P D


APD791-202-Pharmacokinetic NTF, 09 December 2022 
Note to File Template Version 1.0, 28Aug2020 
 
Page 3 of 4                             
Appendix A  Table of Contents of APD791-202 PK Analysis  
14.3.1.1  
Plot of Mean (+/-SD) Plasma Temanogrel Concentrations by Treatment 
on Linear and Semi-log Scale Pharmacokinetic Set 
14.3.1.2 
 Plot of Mean (+/-SD) Plasma AR295980 (M1) Concentrations by Treatment 
on Linear and Semi-log Scale Pharmacokinetic Set 
14.3.1.3  
Plot of Mean (+/-SD) Plasma AR295981 (M2) Concentrations by Treatment 
on Linear and Semi-log Scale Pharmacokinetic Set 
14.3.2.1  
Spaghetti Plot of Individual Plasma Temanogrel Concentrations by 
Treatment on Linear and Semi-log Scale Pharmacokinetic Set 
Temanogrel 20 mg 
14.3.2.2  
Spaghetti Plot of Individual Plasma AR295980 (M1) Concentrations by 
Treatment on Linear and Semi-log Scale Pharmacokinetic Set Temanogrel 
20 mg 
14.3.2.3  
Spaghetti Plot of Individual Plasma AR295981 (M2) Concentrations by 
Treatment on Linear and Semi-log Scale Pharmacokinetic Set Temanogrel 
20 mg 
16.2.5.2.2.1  Plasma Temanogrel Concentration-Time Profiles Pharmacokinetic Set 
16.2.5.2.2.2  Plasma AR295980 (M1) Concentration-Time Profiles Pharmacokinetic Set 
16.2.5.2.2.3  Plasma AR295981 (M2) Concentration-Time Profiles Pharmacokinetic Set 
14.2.6.1.1  
Summary of Plasma Temanogrel Concentrations (ng/mL) by Treatment and 
Timepoint Pharmacokinetic Set 
14.2.6.1.2 
Summary of Plasma AR295980 (M1) Concentrations (ng/mL) by Treatment  
and Timepoint Pharmacokinetic Set 
14.2.6.1.3 
Summary of Plasma AR295981 (M2) Concentrations (ng/mL) by Treatment 
and Timepoint Pharmacokinetic Set 
14.2.6.2.1 
Individual Values and Summary of Plasma Temanogrel Pharmacokinetic 
Parameters by Treatment Pharmacokinetic Set 


APD791-202-Pharmacokinetic NTF, 09 December 2022 
Note to File Template Version 1.0, 28Aug2020 
 
Page 4 of 4                             
14.2.6.2.2
Individual Values and Summary of Plasma AR295980 (M1) 
Pharmacokinetic Parameters by Treatment Pharmacokinetic Set 
14.2.6.2.3 
Individual Values and Summary of Plasma AR295981 (M2) 
Pharmacokinetic Parameters by Treatment Pharmacokinetic Set 
 


 
A P D 7 9 1 -2 0 2 Bi ost atistics  N T F  0 7  Oct o b er 2 0 2 2  
N ot e t o Fil e  T e m pl at e V ersi o n 1. 0, 2 8 A u g 2 0 2 0  
 
P a g e 1  of 3                              
 
N ote t o File  
 
 
D ate:  
0 7  Oct o ber  2 0 2 2  
T o:  
T M F  
Fr o m:   
 
 
 
 
 
Pr ot oc ol N o.:  
A P D 7 9 1 -2 0 2  
S u bject :  
D oc u me nt t he sta t us of bi o metrics-relate d d oc u me nts/ pr ocesses a n d o utli ne pla n 
f or select p ost -data base l oc k safet y a n d efficac y a nal yses 
 
B ac k gr o u n d : 
O n 2 5 A u g ust 2 0 2 2, t he decisi o n was ma de t o disc o nti n ue de vel o p me nt of t he 
Are na car di o vasc ular  pr o gra m s, w hic h i ncl u des A P D 7 9 1 (te ma n o grel) . Enr oll me nt 
i nt o t he o n g oi n g cli nical trial A P D 7 9 1-2 0 2 was ter mi nate d effecti ve i m me diatel y 
a n d st u d y tea m acti vities were re pri oritize d t o f oc us a n d accelerate st u d y cl ose-o ut 
acti vities . F or t his st u d y, t he bi ostatistics , data ma na ge me nt, a n d statistical 
pr o gra m mi n g deli vera bles a n d acti vities are o uts o urce d t o t he cli nical researc h 
or ga nizati o n ( C R O) Me d pace.  
As a res ult of t he i m me diate ter mi nati o n, t he bi ostatistics as pects relate d t o 
fi nalizi n g d oc u me nts (e. g., statistical a nal ysis pla n [ S A P]) a n d ot her d o w nstrea m 
acti vities are eit her i m mat ure a n d/ or ha ve n ot bee n esta blis he d. T hese tas ks w o ul d 
ta ke si g nifica nt ti me a n d res o urces b y b ot h t he Are na a n d Me d p ace tea m t o fi nalize, 
w hic h is n ot feasi ble gi ve n t he accelerate d st u d y cl ose-o ut ti meli ne, w hic h i ncl u des 
t he data base l oc k  ( D B L) pla n ne d f or 1 0  Oct o ber 2 0 2 2 .  
Fi n al St at us : 
 
Statistical A nal ysis Pla n  
 
Draft S A P ( v 0. 3 ) 
 
Statistical A nal ysis Pla n: Ta ble, Listi n g, a n d Fi g ure ( T L F) S hells  
 
Draft T L F s pecificati o ns ( v 0. 2) 
 
C DI S C S pecificati o ns a n d D atasets (a C R F/ S D T M/ A Da M ) 
 
a C R F ( d b C R F; base d o n pr ot oc ol a me n d me nt v 3 . 0) 
 
S D T M : S pecificati o ns a n d datasets b y 2 8 Oct o ber 2 0 2 2  
 
A Da M : Draft s pecificati o ns (R o u n d 1 re vie w b y Are na ) 
 
Statistical A nal ysis Pla n: Ta ble, Listi n g, a n d Fi g ure ( T L F) Pr o gra m mi n g  
 
De vel o p me nt has n ot be g u n f or o ut p ut pr o gra m mi n g  
 
Defi ne. x ml  
 
De vel o p me nt has n ot be g u n f or eit her S D T M or A Da M  Defi nes  
 
 
 
P P D


APD791-202 Biostatistics NTF 07 October 2022
Note to File Template Version 1.0, 28Aug2020
Page 2 of 3                             
Reviewer’s Guide (SDTM/ADaM)

Development has not begun for either SDTM or ADaM Reviewer’s Guides
Unblinding 
Procedure:
Following completion of the DBL sign-off form, the Medpace project statistician 
will circulate the Unblinding form for signature by Arena (Lead Study Statistician, 
Head of Biostatistics and Data Management) and by appropriate Medpace team 
members. The Medpace project statistician will then present both the signed DBL 
and Unblinding forms to the IRT group to document that the unblinded treatment 
assignments could be shared with the Biostatistics team for incorporation into the 
final database. The signed DBL and Unblinding forms will be included in TMF.
Deliverables & 
Analyses:
Since the SAP, CDISC ADaM data, and statistical programming (e.g., dataset level,
table level) will not be finalized, alternative solutions are being utilized to provide 
post-DBL safety and efficacy analyses. No substudy data will be analyzed.
As outlined in protocol Section 10.11, Study APD791-202 was under the purview 
of a Data Safety Monitoring Board (DSMB) and three meetings (Organizational and 
two data review) have been convened. As part of the DSMB process, Open 
(blinded) and Closed (unblinded) Reports were developed and produced by Axio (a 
Cytel company). Arena will be utilizing and augmenting these existing report 
structures in place of SAP-based TLFs for the final report. 
Following DBL, raw datasets, both eCRF (EDC) and external non-CRF, will be 
made available to Axio for production of the unblinded safety and efficacy outputs. 
The table of contents of the final report is contained in Appendix A.
Signatures:
_____________________
Distribution:
☒  TMF or applicable document repository
PPD
PPD
PPD
PPD


 
APD791-202 Biostatistics NTF 07 October 2022 
Note to File Template Version 1.0, 28Aug2020 
 
Page 3 of 3                             
Appendix A – Table of Contents of Final Report 
Randomization ....................................................................................................................................................................................................................................  
Table 1.1.AB: Subject Randomization by Month ......................................................................................................................................................... 
Figure 1.1.AB: Cumulative Randomization by Month ................................................................................................................................................. 
Table 1.2.AB: Subject Randomization by Region and Site .................................................................................................................................................... 
Demographic ......................................................................................................................................................................................................................... 
Table 2.1.AB: Demographic and Baseline Characteristics ..................................................................................................................................................... 
Disposition............................................................................................................................................................................................................................................  
Table 3.1.AB: Subject Disposition ............................................................................................................................................................................................ 
Safety .................................................................................................................................................................................................................................................... 
Table 4.1.AB: Overall Summary of Treatment-Emergent Adverse Events (TEAE) ............................................................................................................ 
Table 4.2.AB: Treatment-Emergent Adverse Events (TEAE) by System Organ Class and Preferred Term .................................................................... 
Table 4.3.AB: Serious Treatment-Emergent Adverse Events (TEAE) by System Organ Class and Preferred Term ...................................................... 
Table 4.4.AB: Grade 3 or Higher Treatment-Emergent Adverse Events (TEAE) by System Organ Class and Preferred Term.................................... 
Table 4.5.AB: Treatment-Emergent Adverse Events (TEAE) Related or Probably Related to Study Treatment by System Organ Class and 
Preferred Term ............................................................................................................................................................................................................................. 
Table 4.6.AB: Treatment-Emergent Adverse Events (TEAE) by BARC Classification ..................................................................................................... 
Table 4.7.AB: Cardiovascular Treatment-Emergent Adverse Events (TEAE) by System Organ Class and Preferred Term ......................................... 
Table 4.8.AB: Treatment-Emergent Adverse Events (TEAE) with Fatal Outcome by System Organ Class and Preferred Term .................................. 
Vitals ..................................................................................................................................................................................................................................................... 
Table 5.1.AB: Summary of Observed and Change from Baseline in Vital Signs ........................................................................................................ 
Figure 2.1.AB: Vital Signs Measurements: Systolic Blood Pressure (mmHg) ..................................................................................................................... 
Figure 2.1.AB: Vital Signs Measurements: Diastolic Blood Pressure (mmHg) .................................................................................................................... 
Figure 2.1.AB: Vital Signs Measurements: Heart Rate (beats/min) ....................................................................................................................................... 
ECGs .....................................................................................................................................................................................................................................  
Table 6.1.AB: Summary of Observed and Change from Baseline in 12-Lead Electrocardiogram Intervals .................................................................... 
Table 6.2.AB: Post-Baseline 12-Lead ECG: Outlier and Morphology Analyses ......................................................................................................... 
Myocardial Injury Markers ...............................................................................................................................................................................................  
Table 7.1.AB: Summary of Observed and Change from Baseline in Myocardial Injury Markers .................................................................................... 
Figure 3.1.1.AB: Subject Level Myocardial Injury Markers: cTnI (µg/L) ............................................................................................................................ 
Figure 3.1.1.AB: Subject Level Myocardial Injury Markers: CK-MB (µg/L) ...................................................................................................................... 
Figure 3.1.1.AB: Subject Level Myocardial Injury Markers: CK (U/L) ............................................................................................................................... 
Figure 3.1.1.AB: Subject Level Myocardial Injury Markers: hs-cTnT (µg/L)...................................................................................................................... 
Figure 3.1.2.AB: Myocardial Injury Markers: cTnI (µg/L) .................................................................................................................................................... 
Figure 3.1.2.AB: Myocardial Injury Markers: CK-MB (µg/L) .............................................................................................................................................. 
Figure 3.1.2.AB: Myocardial Injury Markers: CK (U/L) ........................................................................................................................................................ 
Figure 3.1.2.AB: Myocardial Injury Markers: hs-cTnT (µg/L) .............................................................................................................................................. 
Liver Function ..................................................................................................................................................................................................................................... 
Table 8.1.AB: Summary of Liver Function Tests at 24 Hours Post-PCI/Discharge ............................................................................................................ 
Coronary Physiology  ......................................................................................................................................................................................................................... 
Table 9.1.AB – Part A: Summary of Observed and Change from Baseline in Coronary Physiology Indices .................................................................... 
Table 9.2.AB – Part B: Summary of Observed and Change from Pre PCI in Coronary Physiology Indices ..................................................................... 
Listing .................................................................................................................................................................................................................................................... 
Listing 1.AB: Demographic and Baseline Characteristics ...................................................................................................................................................... 
Listing 2.AB: Subject Disposition ................................................................................................................................................................................. 
Listing 3.AB: Concomitant Medications ....................................................................................................................................................................... 
Listing 4.AB: Medical History ................................................................................................................................................................................................... 
Listing 5.AB: Adverse Events ....................................................................................................................................................................................... 
Listing 6.AB: Vital Signs ............................................................................................................................................................................................... 
Listing 7.AB: 12-Lead Electrocardiogram Intervals ................................................................................................................................................................ 
Listing 8.AB: Listing of Myocardial Injury Markers ............................................................................................................................................................... 
Listing 9.AB: Listing of Liver Function Tests for Any Subjects with Any Abnormal Liver Function Test Result ......................................................... 
Listing 10.AB: Diagnostic Angiography ....................................................................................................................................................................... 
Listing 11.AB: PCI Procedure - Part A ...............................................................................................................................................................  
Listing 11.AB: PCI Procedure - Part B ...............................................................................................................................................................  
Listing 12.AB: Baseline and Post-PCI Angiography Collection ............................................................................................................................................ 
Listing 13.AB: Baseline and Post-PCI Angiography Analysis 
Listing 14.AB: Baseline, Pre-PCI, and Post-PCI Coronary Physiology Indices  ..........................................................................................................